HLA-Ⅱ类基因与中国汉族人白癜风及其临床特征的相关性研究
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摘要
研究背景：白癜风是一种常见的色素脱失性皮肤疾病,通常由于皮肤和毛发内的黑色素细胞选择性破坏所致。白癜风的发病率范围由0.1%到2.9%,在不同种族和地域之间存在显著的差异性。该病虽然不会危及生命,但对患者的身心健康造成巨大的负面影响。白癜风多发生于儿童或青年,约一半患者于20岁以前发病,因此通常以白癜风发病年龄20岁为界,将其分为早发型白癜风(Early-onset vitiligo)和晚发型白癜风(Late-onset vitiligo).临床和流行病学调查研究均表明白癜风遵循一种多基因遗传模式。白癜风发病机制目前尚未明确,目前提出的一些相关假设主要包括黑素细胞自身破坏学说、生物化学、神经起源学说、自身免疫和遗传学说。在过去的十多年,自身免疫学说主要源于在流行病学研究中发现白癜风患者及其亲属常伴发其他自身免疫性疾病,如自身免疫性甲状腺病、风湿性关节炎、银屑病、成人胰岛素依赖型糖尿病、恶性贫血、阿狄森氏病和系统性红斑狼疮。人类白细胞抗原(HLA)是目前公认的在各类自身免疫性疾病的易感性中发挥重要作用的影响因素,与白癜风发病相关的部分遗传因素也主要集中于HLA系统。既往在不同人群的白癜风研究中,多数报道其发病与HLA-II类基因相关,但很少有研究可获得一致的关联证据,可能与遗传效应微弱,基因间、基因与环境间复杂的交互作用,人群分层或不同人群间的遗传差异性有关。通过对以往研究结果的重新分析,发现在HLA-Ⅱ类基因中,DRB1*07一直显示与中国汉族人白癜风有显著相关性。有趣的是,有报道发现HLA-DR在白癜风皮损周围的表皮内表达异常,提示其可能在HLA-II类基因限制性黑素细胞的死亡中发挥作用。最近,也有一些研究发现携带HLA-II类基因／单倍型的个体,其白癜风的发病年龄更早,更易伴发自身免疫性疾病,家族史的发生率更高。
目的：(1)进一步探寻HLA-II类基因在中国汉族人群中与白癜风的相关性。(2)评估HLA-II类基因对中国汉族人白癜风各临床特征的遗传效应。
方法：采用多聚酶链反应(PCR)／序列特异引物的方法,探寻HLA-DRB1*07等位基因在1178例彼此间无血缘关系的白癜风患者和1743例健康对照中的分布情况,观察HLA-DRB1*07等位基因阳性的白癜风患者和HLA-DRB1*07阴性患者间临床特征的差异性。
结果：(1)白癜风病例中HLA-DRB1*07阳性的比例较对照中HLA-DRB1*07阳性的比例显著增高(40.75％vs.25.83％,OR:1.97,95％CI1.68-2.31,P=2.13×10-17).病例和对照中DRB1*07阳性等位基因频率分别为0.20和0.13。在所有白癜风病例中,有480例为DRB1*07日性,剩余的698例患者则为DRB1*07阴性。在病例组中,DRB1*07日性患者的平均年龄为25.57±14.45岁,而DRB1*07阴性患者的平均年龄为27.43±14.71岁(P=0.031)。男女性别比例在白癜风病例的DRB1*07阳性和阴性两组间未见显著差别(P=0.099).(2)HLA-DRB1*07阳性的白癜风患者比DRB1*07阴性患者的发病年龄更早。HLA-DRB1*07阳性的白癜风患者的发病年龄中位数为17.00±16.00岁,HLA-DRB1*07阴性的白癜风患者的发病年龄中位数为19.00±18.00,两者之间存在显著性差异(P=0.004)。在DRB1*07阳性患者中,早发型白癜风的频率也较阴性患者中显著增高(65.14％vs.55.59％,P=0.001,OR=1.49,95％CI1.17-1.90).(3)DRB1*07阳性的白癜风患者较DRB1*07阴性患者的家族史发生率更高。在DRB1*07阳性的白癜风患者中,约30.8%具有家族史,而仅有23.6%的DRB1*07阴性患者有家族史(OR=1.44.95％CI1.11-1.87,P=0.006).(4)与DRB1*07阴性的白癜风患者相比,DRB1*07阳性患者患自身免疫性疾病的频率较高(4.0%vs32%),然而,两组间的频率差别未达到统计学的显著性水平(OR=1.27,95％CI0.68-2.37,P=0.458)
结论：(1)HLA-II类基因与中国汉族人白癜风存在显著的关联性。(2)中国汉族人白癜风HLA-DRB1*07阳性的患者与HLA*DRB1*07阴性患者的临床特征有明显的差异,HLA-DRB1*07阳性白癜风患者较阴性患者的发病年龄更早,家族史发生率更高。(3)本研究提示自身免疫易感性相关的遗传因素可能在白癜风的一些临床特征或临床亚型的发病机制中发挥重要作用。
Background:Vitiligo is a common depigmentary disorder resulting from selective destruction of melanocytes in the skin and hair, with diverse prevalence rates ranging from0.1%to2.9%in different geographic regions and ethnic groups. Although non-fatal, vitiligo could cause severe negative psychosocial impact on the individuals affected. Vitiligo usually begins in childhood or young adulthood, with approximately half of the patients having onset before the age of20years. Therefore, patients with onset at20years or younger were classified as early-onset vitiligo, while patients with onset older than20years were classified as late-onset vitiligo. Clinical and epidemiological investigations indicated that vitiligo might follow a pattern of polygenetic or multifactorial inheritance, and several hypotheses of which most are unproved so far, have been proposed to explain the pathogenesis of vitiligo, including self-destructive, biochemical, neural, autoimmune and genetic hypotheses. In the past decades, the autoimmune hypothesis had received the most attention based partly on the frequent occurrence of other autoimmune diseases in vitiligo patients and their relatives including autoimmune thyroid disease, rheumatoid arthritis, psoriasis, adult-onset insulin-dependent diabetes mellitus, pernicious anaemia, Addison's disease and systemic lupus erythematosus. The human leucocyte antigen (HLA) is now recognized as a major contributing factor for susceptibility to a variety of autoimmune diseases, and numerous associations with vitiligo have focused on the HLA system. Most of them reported multiple HLA class II alleles to be associated with vitiligo in different populations; however, a few studies had consistent association evidence, which might be explained by weak genetic effects or complex gene-gene or gene-environmental interactions, population stratification or genetic differences between populations. Of HLA class II alleles, DRB1*07has consistently shown a positive association with vitiligo in Chinese Han population through reanalysis of previous studies. Interestingly, abnormal expression of HLA-DR in perilesional epidermis has also been reported and was suggested to contribute to HLA class II-restricted melanocyte killing. Recently, several studies have further suggested that HLA class II alleles/haplotypes have been inclined towards patients who have earlier-onset age, with autoimmune diseases or with family history.
Objective:(1) To further explore the relationship between HLA class II gene and vitiligo in Chinese Han population.(2) To evaluate the HLA class II gene effect on the clinical features of vitiligo in Chinese Han population.
Methods:This study investigated DRB1*07allele distribution in1178unrelated Chinese vitiligo patients and1743healthy controls using polymerase chain reaction/sequence specific primer method and observed clinical differences between DRB1*07positive and DRB1*07negative patients.
Results:(1) A significant proportion of patients were DRB1*07positive compared with the control group (40.75%vs.25.83%, OR=1.97,95%CI1.68-2.31, P=2.13×10-17). The DRB1*07positive allele of case and control were0.20and0.13respectively. Of all the patients,480were DRB1*07positive and the remaining698patients were DRB1*07negative. The mean age was25.57±14.45year in DRB1*07positive group and27.43±14.71year in DRB1*07negative group (P=0.031). The gender distribution showed an approximately equal proportion in the two groups (P=0.099).(2) DRB1*07positive patients have an earlier disease onset than DRB1*07negative patients, the median age of onset being17.00±16.00year vs.19.00±18.00year for DRB1*07positive and DRB1*07negative patients respectively (P=0.004).The frequency of early-onset vitiligo was also significantly higher in DRB1*07positive patients than DRB1*07negative patients (65.14%vs.55.59%, P=0.001, OR=1.49,95%CI1.17-1.90).(3) Family history of vitiligo was more common in DRB1*07positive patients than in DRB1*07negative patients. There were30.8%patients with positive family history in DRB1*07positive group, compared with23.6%patients in DRB1*07negative group (OR=1.44,95%CI1.11-1.87, P=0.006).(4) The DRB1*07positive group showed increased frequency of autoimmune diseases compared with DRB1*07negative group (4.0%vs.3.2%), however, the difference did not reach significant level (OR=1.27,95%CI0.68-2.37, P=0.458).
Conclusions:(1) The HLA class II gene showed significant association with vitiligo in Chinese Han population.(2) This study confirmed that DRB1*07positive patients had some obvious clinical differences (with earlier-onset age and family history) from DRB1*07negative patients in the Chinese Han population.(3) This study provides evidence that genetic component of autoimmune susceptibility might play a key role in the pathogenesis of some clinical features or subtypes of vitiligo.
目的：(1)进一步探寻HLA-II类基因在中国汉族人群中与白癜风的相关性。(2)评估HLA-II类基因对中国汉族人白癜风各临床特征的遗传效应。
方法：采用多聚酶链反应(PCR)／序列特异引物的方法,探寻HLA-DRB1*07等位基因在1178例彼此间无血缘关系的白癜风患者和1743例健康对照中的分布情况,观察HLA-DRB1*07等位基因阳性的白癜风患者和HLA-DRB1*07阴性患者间临床特征的差异性。
结果：(1)白癜风病例中HLA-DRB1*07阳性的比例较对照中HLA-DRB1*07阳性的比例显著增高(40.75％vs.25.83％,OR:1.97,95％CI1.68-2.31,P=2.13×10-17).病例和对照中DRB1*07阳性等位基因频率分别为0.20和0.13。在所有白癜风病例中,有480例为DRB1*07日性,剩余的698例患者则为DRB1*07阴性。在病例组中,DRB1*07日性患者的平均年龄为25.57±14.45岁,而DRB1*07阴性患者的平均年龄为27.43±14.71岁(P=0.031)。男女性别比例在白癜风病例的DRB1*07阳性和阴性两组间未见显著差别(P=0.099).(2)HLA-DRB1*07阳性的白癜风患者比DRB1*07阴性患者的发病年龄更早。HLA-DRB1*07阳性的白癜风患者的发病年龄中位数为17.00±16.00岁,HLA-DRB1*07阴性的白癜风患者的发病年龄中位数为19.00±18.00,两者之间存在显著性差异(P=0.004)。在DRB1*07阳性患者中,早发型白癜风的频率也较阴性患者中显著增高(65.14％vs.55.59％,P=0.001,OR=1.49,95％CI1.17-1.90).(3)DRB1*07阳性的白癜风患者较DRB1*07阴性患者的家族史发生率更高。在DRB1*07阳性的白癜风患者中,约30.8%具有家族史,而仅有23.6%的DRB1*07阴性患者有家族史(OR=1.44.95％CI1.11-1.87,P=0.006).(4)与DRB1*07阴性的白癜风患者相比,DRB1*07阳性患者患自身免疫性疾病的频率较高(4.0%vs32%),然而,两组间的频率差别未达到统计学的显著性水平(OR=1.27,95％CI0.68-2.37,P=0.458)
结论：(1)HLA-II类基因与中国汉族人白癜风存在显著的关联性。(2)中国汉族人白癜风HLA-DRB1*07阳性的患者与HLA*DRB1*07阴性患者的临床特征有明显的差异,HLA-DRB1*07阳性白癜风患者较阴性患者的发病年龄更早,家族史发生率更高。(3)本研究提示自身免疫易感性相关的遗传因素可能在白癜风的一些临床特征或临床亚型的发病机制中发挥重要作用。
Background:Vitiligo is a common depigmentary disorder resulting from selective destruction of melanocytes in the skin and hair, with diverse prevalence rates ranging from0.1%to2.9%in different geographic regions and ethnic groups. Although non-fatal, vitiligo could cause severe negative psychosocial impact on the individuals affected. Vitiligo usually begins in childhood or young adulthood, with approximately half of the patients having onset before the age of20years. Therefore, patients with onset at20years or younger were classified as early-onset vitiligo, while patients with onset older than20years were classified as late-onset vitiligo. Clinical and epidemiological investigations indicated that vitiligo might follow a pattern of polygenetic or multifactorial inheritance, and several hypotheses of which most are unproved so far, have been proposed to explain the pathogenesis of vitiligo, including self-destructive, biochemical, neural, autoimmune and genetic hypotheses. In the past decades, the autoimmune hypothesis had received the most attention based partly on the frequent occurrence of other autoimmune diseases in vitiligo patients and their relatives including autoimmune thyroid disease, rheumatoid arthritis, psoriasis, adult-onset insulin-dependent diabetes mellitus, pernicious anaemia, Addison's disease and systemic lupus erythematosus. The human leucocyte antigen (HLA) is now recognized as a major contributing factor for susceptibility to a variety of autoimmune diseases, and numerous associations with vitiligo have focused on the HLA system. Most of them reported multiple HLA class II alleles to be associated with vitiligo in different populations; however, a few studies had consistent association evidence, which might be explained by weak genetic effects or complex gene-gene or gene-environmental interactions, population stratification or genetic differences between populations. Of HLA class II alleles, DRB1*07has consistently shown a positive association with vitiligo in Chinese Han population through reanalysis of previous studies. Interestingly, abnormal expression of HLA-DR in perilesional epidermis has also been reported and was suggested to contribute to HLA class II-restricted melanocyte killing. Recently, several studies have further suggested that HLA class II alleles/haplotypes have been inclined towards patients who have earlier-onset age, with autoimmune diseases or with family history.
Objective:(1) To further explore the relationship between HLA class II gene and vitiligo in Chinese Han population.(2) To evaluate the HLA class II gene effect on the clinical features of vitiligo in Chinese Han population.
Methods:This study investigated DRB1*07allele distribution in1178unrelated Chinese vitiligo patients and1743healthy controls using polymerase chain reaction/sequence specific primer method and observed clinical differences between DRB1*07positive and DRB1*07negative patients.
Results:(1) A significant proportion of patients were DRB1*07positive compared with the control group (40.75%vs.25.83%, OR=1.97,95%CI1.68-2.31, P=2.13×10-17). The DRB1*07positive allele of case and control were0.20and0.13respectively. Of all the patients,480were DRB1*07positive and the remaining698patients were DRB1*07negative. The mean age was25.57±14.45year in DRB1*07positive group and27.43±14.71year in DRB1*07negative group (P=0.031). The gender distribution showed an approximately equal proportion in the two groups (P=0.099).(2) DRB1*07positive patients have an earlier disease onset than DRB1*07negative patients, the median age of onset being17.00±16.00year vs.19.00±18.00year for DRB1*07positive and DRB1*07negative patients respectively (P=0.004).The frequency of early-onset vitiligo was also significantly higher in DRB1*07positive patients than DRB1*07negative patients (65.14%vs.55.59%, P=0.001, OR=1.49,95%CI1.17-1.90).(3) Family history of vitiligo was more common in DRB1*07positive patients than in DRB1*07negative patients. There were30.8%patients with positive family history in DRB1*07positive group, compared with23.6%patients in DRB1*07negative group (OR=1.44,95%CI1.11-1.87, P=0.006).(4) The DRB1*07positive group showed increased frequency of autoimmune diseases compared with DRB1*07negative group (4.0%vs.3.2%), however, the difference did not reach significant level (OR=1.27,95%CI0.68-2.37, P=0.458).
Conclusions:(1) The HLA class II gene showed significant association with vitiligo in Chinese Han population.(2) This study confirmed that DRB1*07positive patients had some obvious clinical differences (with earlier-onset age and family history) from DRB1*07negative patients in the Chinese Han population.(3) This study provides evidence that genetic component of autoimmune susceptibility might play a key role in the pathogenesis of some clinical features or subtypes of vitiligo.
引文
1 Spritz RA. The genetics of generalized vitiligo. Curr Dir Autoimmun 2008; 10: 244-257.
2 Zhang XJ, Chen JJ, Liu JB. The genetic concept of vitiligo. J Dermatol Sci 2005; 39:137-146.
3 Orozco-Topete R, Cordova-Lopez J, Yamamoto-Furusho JK et al. HLA-DRB1 *04 is associated with the genetic susceptibility to develop vitiligo in Mexican patients with autoimmune thyroid disease. J Am Acad Dermatol 2005; 52: 182-183.
4 Fain PR, Babu SR, Bennett DC et al. HLA class II haplotype DRB1*04-DQB1*0301 contributes to risk of familial generalized vitiligo and early disease onset. Pigment Cell Res 2006; 19:51-57.
5 Misri R, Khopkar U, Shankarkumar U et al. Comparative case control study of clinical features and human leukocyte antigen susceptibility between familial and nonfamilial vitiligo. Indian J Dermatol Venereol Leprol 2009; 75:583-587.
6 陈竺.医学遗传学.北京：人民卫生出版社.2001.
7 Risch N, Merikangas K. The future of genetic studies of complex human diseases. Science 1996; 273:1516-1517.
8 沈岩.人类疾病基因的识别——机遇与挑战.中国医学科学院学报 2005;27：263-264.
9 Lander ES, Linton LM, Birren B et al. Initial sequencing and analysis of the human genome. Nature 2001; 409:860-921.
10 Kruglyak L, Nickerson DA. Variation is the spice of life. Nat Genet 2001; 27: 234-236.
11 Sachidanandam R, Weissman D, Schmidt SC et al. A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature 2001; 409:928-933.
12 Quan C, Ren YQ, Xiang LH et al. Genome-wide association study for vitiligo identifies susceptibility loci at 6q27 and the MHC. Nat Genet; 42:614-618.
13 Zhang XJ, Huang W, Yang S et al. Psoriasis genome-wide association study identifies susceptibility variants within LCE gene cluster at 1q21. Nat Genet 2009; 41:205-210.
14 Han JW, Zheng HF, Cui Y et al. Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus. Nat Genet 2009; 41:1234-1237.
15 Zhang FR, Huang W, Chen SM et al. Genomewide association study of leprosy. NEngl J Med 2009; 361:2609-2618.
16 Wang LD, Zhou FY, Li XM et al. Genome-wide association study of esophageal squamous cell carcinoma in Chinese subjects identifies susceptibility loci at PLCE1 and C20orf54. Nat Genet,42:759-763.
17 Das SK. Majumder PP, Chakraborty R et al. Studies on vitiligo. I. Epidemiological profile in Calcutta, India. Genet Epidemiol 1985; 2:71-78.
18 Birlea SA, Fain PR, Spritz RA. A Romanian population isolate with high frequency of vitiligo and associated autoimmune diseases. Arch Dermatol 2008; 144:310-316.
19 Taieb A, Picardo M. Clinical practice. Vitiligo. N Engl J Med 2009; 360: 160-169.
20 Jacobson DL, Gange SJ, Rose NR et al. Epidemiology and estimated population burden of selected autoimmune diseases in the United States. Clin Immunol Immunopathol 1997; 84:223-243.
21 Mehta NR, Shah KC, Theodore C et al. Epidemiological study of vitiligo in Surat area, South Gujarat. Indian J Med Res 1973; 61:145-154.
22 Howitz J, Brodthagen H, Schwartz M et al. Prevalence of vitiligo. Epidemiological survey on the Isle of Bornholm. Denmark. Arch Dermatol 1977; 113:47-52.
23 Shajil EM, Chatterjee S, Agrawal D et al. Vitiligo:pathomechanisms and genetic polymorphism of susceptible genes. Indian J Exp Biol 2006; 44: 526-539.
24 Majumder PP. Genetics and prevalence of vitiligo vulgaris. In:Vitiligo (Harm SK, Nordlund JJ, eds). Oxford:Blackwell Science.2000; 18-20.
25 李凤岐,倪容之,蒋仲元.南京地区白癜风流行病学调查报告.中华皮肤科杂志 1987；20：332-333.
26 崔建,沈丽玉,王光超.450例白癜风临床分析.临床皮肤科杂志 1989；18：123-125.
27 孙廷泉,牛立军,刘涛.山东泰安地区白癜风流行病学调查报告.皮肤病与性病 1999；21：25-26.
28 徐元勇,叶冬青,童志才et al.安徽省宿州地区农村居民四种皮肤病流行病学调查.中华皮肤科杂志 2002；35：406-407.
29 Dogra S. Parsad D, Handa S et al. Late onset vitiligo:a study of 182 patients. M J Dermatol 2005; 44:193-196.
30 张学军.皮肤性病学,第6版edn.北京：人民卫生出版社.2004.
31 Hamm SK, Nordlund JJ. Vitiligo. Oxford:Blackwell Science.2000.
32 杨国亮,王侠生,eds.现代皮肤病学,1 edn.上海：上海医科大学出版社.1996.
33 Westerhof W, d'Ischia M. Vitiligo puzzle:the pieces fall in place. Pigment Cell Res 2007; 20:345-359.
34 Schallreuter KU, Bahadoran P, Picardo M et al. Vitiligo pathogenesis: autoimmune disease, genetic defect, excessive reactive oxygen species, calcium imbalance, or what else? Exp Dermatol 2008; 17:139-140; discussion 141-160.
35 Majumder PP, Das SK, Li CC. A genetical model for vitiligo. Am J Hum Genet 1988; 43:119-125.
36 Hafez M. Sharaf L, Abd el-Nabi SM. The genetics of vitiligo. Acta Derm Venereol 1983; 63:249-251.
37 Nath SK, Majumder PP, Nordlund JJ. Genetic epidemiology of vitiligo: multilocus recessivity cross-validated. Am J Hum Genet 1994; 55:981-990.
38 Zhang XJ, Liu JB, Gui JP et al. Characteristics of genetic epidemiology and genetic models for vitiligo. J Am Acad Dermatol 2004; 51:383-390.
39 Alkhateeb A, Fain PR, Thody A et al. Epidemiology of vitiligo and associated autoimmune diseases in Caucasian probands and their families. Pigment Cell Res 2003; 16:208-214.
40 Venkataram MN, White AG, Leeny WA et al. HLA antigens in Omani patients with vitiligo. Clin Exp Dermatol 1995; 20:35-37.
41 Majumder PP. Nordlund JJ, Nath SK. Pattern of familial aggregation of vitiligo. Arch Dermatol 1993; 129:994-998.
42 高天文,李强,李春英et al.白癜风2008例临床分析.中国皮肤性病学杂志 2002；16：304-306.
43 朱光斗.白癜风病因的初步探讨.临床皮肤科杂志 1990；19：9-11.
44 桂金萍,李玉珍,李进先et al.11080例白癜风患者及其家系分析.中华皮肤科杂志 2001：34：140.
45 马宏裕,倪修年,徐树平et al.1808例白癜风临床资料与分型研究.临床皮肤科杂志 2000；29：280-281.
46 孙越,韩菁,朱光斗.白癜风150例家系调查.临床皮肤科杂志 2000；29：149-150.
47 Spritz RA. The genetics of generalized vitiligo and associated autoimmune diseases. Pigment Cell Res 2007; 20:271-278.
48 Rezaei N, Gavalas NG, Weetman AP et al. Autoimmunity as an aetiological factor in vitiligo. J Eur Acad Dermatol Venereol 2007; 21:865-876.
49 Nath SK, Kelly JA, Namjou B et al. Evidence for a susceptibility gene, SLEV1, on chromosome 17p13 in families with vitiligo-related systemic lupus erythematosus. Am J Hum Genet 2001; 69:1401-1406.
50 Jin Y, Mailloux CM, Go wan K et al. NALP1 in vitiligo-associated multiple autoimmune disease. N Engl J Med 2007; 356:1216-1225.
51 Alkhateeb A, Stetler GL, Old W et al. Mapping of an autoimmunity susceptibility locus (AIS1) to chromosome 1p31.3-p32.2. Hum Mol Genet 2002; 11:661-667.
52 Alkhateeb A, Fain PR, Spritz RA. Candidate functional promoter variant in the FOXD3 melanoblast developmental regulator gene in autosomal dominant vitiligo. J Invest Dermatol 2005; 125:388-391.
53 Fain PR, Gowan K, LaBerge GS et al. A genomewide screen for generalized vitiligo:confirmation of AIS1 on chromosome 1p31 and evidence for additional susceptibility loci. Am J Hum Genet 2003; 72:1560-1564.
54 Spritz RA, Gowan K, Bennett DC et al. Novel vitiligo susceptibility loci on chromosomes 7 (AIS2) and 8 (AIS3), confirmation of SLEV1 on chromosome 17, and their roles in an autoimmune diathesis. Am J Hum Genet 2004:74: 188-191.
55 Horuk R, Yansura DG, Reilly D et al. Purification, receptor binding analysis, and biological characterization of human melanoma growth stimulating activity (MGSA). Evidence for a novel MGSA receptor. J Biol Chem 1993; 268: 541-546.
56 Her C, Aksoy IA, Kimura S et al. Human estrogen sulfotransferase gene (STE): cloning, structure, and chromosomal localization. Genomics 1995; 29:16-23.
57 Chen JJ, Huang W, Gui JP et al. A novel linkage to generalized vitiligo on 4q13-q21 identified in a genomewide linkage analysis of Chinese families. Am J Hum Genet 2005:76:1057-1065.
58 Liang Y. Yang S, Zhou Y et al. Evidence for two susceptibility loci on chromosomes 22q12 and 6p21-p22 in Chinese generalized vitiligo families. J Invest Dermatol 2007; 127:2552-2557.
59 Hirschhorn JN. Genomewide association studies--illuminating biologic pathways. N Engl J Med 2009; 360:1699-1701.
60 Donnelly P. Progress and challenges in genome-wide association studies in humans. Nature 2008; 456:728-731.
61 Birlea SA, Gowan K, Fain PR et al. Genome-wide association study of generalized vitiligo in an isolated European founder population identifies SMOC2, in close proximity to IDDM8. J Invest Dermatol 2009; 130:798-803.
62 肖毅,赵玉铭,宋芳吉et al. HLA-DRB1等位基因与中国北方汉族白癜风的相关性.中华皮肤科杂志 2000;33：5-7.
63 Tastan HB, Akar A, Orkunoglu FE et al. Association of HLA class I antigens and HLA class II alleles with vitiligo in a Turkish population. Pigment Cell Res 2004; 17:181-184.
64 Ren Y, Yang S, Xu S et al. Genetic variation of promoter sequence modulates XBP1 expression and genetic risk for vitiligo. PLoS Genet 2009; 5:e1000523.
65 Iacovelli P, Sinagra JL, Vidolin AP et al. Relevance of thyroiditis and of other autoimmune diseases in children with vitiligo. Dermatology 2005; 210:26-30.
66 Zhang Z, Xu SX, Zhang FY et al. The analysis of genetics and associated autoimmune diseases in Chinese vitiligo patients. Arch Dermatol Res 2009; 301: 167-173.
67 Le Poole IC, Wankowicz-Kalinska A, van den Wijngaard RM et al. Autoimmune aspects of depigmentation in vitiligo. J Investig Dermatol Symp Proc 2004: 9:68-72.
68 Park YK, Kim NS, Hann SK et al. Identification of autoantibody to melanocytes and characterization of vitiligo antigen in vitiligo patients. J Dermatol Sci 1996; 11:111-120.
69 Yee C, Thompson JA, Roche P et al. Melanocyte destruction after antigen-specific immunotherapy of melanoma:direct evidence of t cell-mediated vitiligo. J Exp Med 2000; 192:1637-1644.
70 Arcos-Burgos M, Parodi E, Salgar M et al. Vitiligo:complex segregation and linkage disequilibrium analyses with respect to microsatellite loci spanning the HLA. Hum Genet 2002; 110:334-342.
71 Schwartz DW, Felser B, Mayr WR. The genetics of HLA. Folia Biol (Praha) 1995; 41:123-139.
72 Helmuth R, Fildes N, Blake E et al. HLA-DQ alpha allele and genotype frequencies in various human populations, determined by using enzymatic amplification and oligonucleotide probes. Am J Hum Genet 1990; 47:515-523.
73 Gao X, Bhatia K, Trent RJ et al. HLA-DR,DQ nucleotide sequence polymorphisms in five Melanesian populations. Tissue Antigens 1992:40: 31-37.
74 Arnaiz-Villena A, Benmamar D, Alvarez M et al. HLA allele and haplotype frequencies in Algerians. Relatedness to Spaniards and Basques. Hum Immunol 1995; 43:259-268.
75 Zamani M, Spaepen M, Sghar SS et al. Linkage and association of HLA class Ⅱ genes with vitiligo in a Dutch population. Br J Dermatol 2001; 145:90-94.
76 A a-F, M a-A, F F. Study of HLA class Ⅰ/Ⅱ and T lymphocyte subsets in Kuwaiti vitiligo patients. Eur J Immunogenet 1995; 22:209-213.
77 Schallreuter KU, Levenig C, Kuhnl P et al. Histocompatibility antigens in vitiligo:Hamburg study on 102 patients from northern Germany. Dermatology 1993;187:186-192.
78 G O, L P, P M. Vitiligo is associated with a significant increase in HLA-A30, Cw6 and DQw3 and a decrease in C4AQ0 in northern Italian patients. Dermatology 1992; 185:123-127.
79 Buc M, Fazekasova H, Cechova E et al. Occurrence rates of HLA-DRB1, HLA-DQB1, and HLA-DPB1 alleles in patients suffering from vitiligo. Eur J Dermatol 1998; 8:13-15.
80 王珺赵,王岩,et al..北方汉族泛发型白癜风与HLA I 、 II类等位基因相关性研究.中华医学遗传学杂志 2007；24：221-223.
81 Liu JB, Li M, Chen H et al. Association of vitiligo with HLA-A2:a meta-analysis. J Eur Acad Dermatol Venereol 2007; 21:205-213.
82 Zhang XJ. Liu HS, Liang YH et al. Association of HLA class I alleles with vitiligo in Chinese Hans. J Dermatol Sci 2004; 35:165-168.
83 Yang S, Wang JY, Gao M et al. Association of HLA-DQA1 and DQB1 genes with vitiligo in Chinese Hans. Int J Dermatol 2005; 44:1022-1027.
84 Olerup O, Zetterquist H. HLA-DR typing by PCR amplification with sequence-specific primers (PCR-SSP) in 2 hours:an alternative to serological DR typing in clinical practice including donor-recipient matching in cadaveric transplantation. Tissue Antigens 1992; 39:225-235.
85 赵桐茂.骨髓库和脐血库中的HLA分型技术和策略.中国输血杂志 2001；14：382-385.
86 Taurog JD. The role of HLA-B27 in spondyloarthritis. J Rheumatol; 37: 2606-2616.
87 Thursz MR, Kwiatkowski D, Allsopp CE et al. Association between an MHC class II allele and clearance of hepatitis B virus in the Gambia. N Engl J Med 1995; 332:1065-1069.
88 Hill AV, Allsopp CE, Kwiatkowski D et al. Common west African HLA antigens are associated with protection from severe malaria. Nature 1991; 352: 595-600.
89 Thursz M, Yallop R, Goldin R et al. Influence of MHC class II genotype on outcome of infection with hepatitis C virus. The HENCORE group. Hepatitis C European Network for Cooperative Research. Lancet 1999; 354:2119-2124.
90 Dunstan SJ, Stephens HA, Blackwell JM et al. Genes of the class II and class III major histocompatibility complex are associated with typhoid fever in Vietnam. J Infect Dis 2001; 183:261-268.
91 Rossman MD, Thompson B, Frederick M et al. HLA-DRB1*1101:a significant risk factor for sarcoidosis in blacks and whites. Am J Hum Genet 2003:73:720-735.
92 Lang HL, Jacobsen H. Ikemizu S et al. A functional and structural basis for TCR cross-reactivity in multiple sclerosis. Nat Immunol 2002; 3:940-943.
93 Xiao Y ZY, Song FJ. Association of HLA-DRB1 alleles with generalized vitiligo in Chinese Hans in north China. Chinese J Dermatol 2000; 33:5-7.
94 Wang J, Zhao YM, Wang Y et al. Association of HLA class I and II alleles with generalized vitiligo in Chinese Hans in north China. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2007; 24:221-223.
95 Wang XY JR, Zhu MJ.. Association of HLA-DRB1 alleles with vitiligo and psoriasis vulgaris in Chinese Han people of Jilin region. Chinese J Immunol 2008; 28:144-146.
96 al Badri AM, Foulis AK, Todd PM et al. Abnormal expression of MHC class II and ICAM-1 by melanocytes in vitiligo. J Pathol 1993; 169:203-206.
97 Le Poole IC, van den Wijngaard RM, Westerhof W et al. Presence of T cells and macrophages in inflammatory vitiligo skin parallels melanocyte disappearance. Am J Pathol 1996; 148:1219-1228.
98 van den Wijngaard R. Wankowicz-Kalinska A, Le Poole C et al. Local immune response in skin of generalized vitiligo patients. Destruction of melanocytes is associated with the prominent presence of CLA+T cells at the perilesional site. Lab Invest 2000; 80:1299-1309.
99 Dawber RP. Vitiligo in mature-onset diabetes mellitus. Br J Dermatol 1968; 80: 275-278.
100 Sharma VK, Dawn G, Kumar B. Profile of alopecia areata in Northern India.Int J Dermatol 1996; 35:22-27.
101 Allison JR, Jr., Curtis AC. Vitiligo and pernicious anemia. AMA Arch Derm 1955; 72:407-408.
102 Dawber RP. Integumentary associations of pernicious anaemia. Br J Dermatol 1970; 82:221-223.
103 Grunnet I, Howitz J, Reymann F et al. Vitiligo and pernicious anemia. Arch Dermatol 1970; 101:82-85.
104 Koshiyama H, Ito M, Yoshinami N et al. Two cases of asymptomatic adrenocortical insufficiency with autoimmune thyroid disease. Endocr J 1994; 41:373-378.
105 Schallreuter KU, Lemke R, Brandt O et al. Vitiligo and other diseases: coexistence or true association? Hamburg study on 321 patients. Dermatology 1994; 188:269-275.
106 Kong MF, Jeffcoate W. Eighty-six cases of Addison's disease. Clin Endocrinol (Oxf) 1994; 41:757-761.
107 Meecham J, Jones EW. Addison's disease and Addisonian anaemia. Lancet 1967; 1:535-538.
108 Dunston GM, Halder RM. Vitiligo is associated with HLA-DR4 in black patients. A preliminary report. Arch Dermatol 1990; 126:56-60.
109 Zhang X, Wang H. Te-Shao H et al. The genetic epidemiology of psoriasis vulgaris in Chinese Han. Int J Dermatol 2002; 41:663-669.
1 Bale SJ, Dracopoli NC, Tucker MA et al. Mapping the gene for hereditary cutaneous malignant melanoma-dysplastic nevus to chromosome 1p. N Engl J Med 1989; 320:1367-1372.
2 Gillanders E, Juo SH, Holland EA et al. Localization of a novel melanoma susceptibility locus to 1p22. Am J Hum Genet 2003; 73:301-313.
3 Hussein MR, Roggero E, Tuthill RJ et al. Identification of novel deletion Loci at 1p36 and 9p22-21 in melanocytic dysplastic nevi and cutaneous malignant melanomas. Arch Dermatol 2003; 139:816-817.
4 Kefford RF,Newton Bishop JA, Bergman W et al. Counseling and DNA testing for individuals perceived to be genetically predisposed to melanoma:A consensus statement of the Melanoma Genetics Consortium. J Clin Oncol 1999: 17:3245-3251.
5 Goldstein AM, Chan M. Harland M et al. High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL. Cancer Res 2006; 66:9818-9828.
6 Epstein EH. Basal cell carcinomas:attack of the hedgehog. Nat Rev Cancer 2008; 8:743-754.
7 Rees JL. Genetics of hair and skin color. Annu Rev Genet 2003:37:67-90.
8 Rees JL. The genetics of sun sensitivity in humans. Am J Hum Genet 2004; 75: 739-751.
9 Bastiaens MT, ter Huurne JA, Kielich C et al. Melanocortin-1 receptor gene variants determine the risk of nonmelanoma skin cancer independently of fair skin and red hair. Am J Hum Genet 2001; 68:884-894.
10 Box NF, Duffy DL, Irving RE et al. Melanocortin-1 receptor genotype is a risk factor for basal and squamous cell carcinoma. J Invest Dermatol 2001:116: 224-229.
11 Kennedy C, ter Huurne J, Berkhout M et al. Melanocortin 1 receptor (MC1R) gene variants are associated with an increased risk for cutaneous melanoma which is largely independent of skin type and hair color. J Invest Dermatol 2001; 117:294-300.
12 Landi MT, Kanetsky PA, Tsang S et al. MC1R, ASIP, and DNA repair in sporadic and familial melanoma in a Mediterranean population. J Natl Cancer Inst 2005;97:998-1007.
13 Liboutet M, Portela M, Delestaing G et al. MC1R and PTCH gene polymorphism in French patients with basal cell carcinomas. J Invest Dermatol 2006: 126:1510-1517.
14 Matichard E, Verpillat P, Meziani R et al. Melanocortin 1 receptor (MC1R) gene variants may increase the risk of melanoma in France independently of clinical risk factors and UV exposure. J Med Genet 2004; 41:e13.
15 Palmer JS, Duffy DL, Box NF et al. Melanocortin-1 receptor polymorphisms and risk of melanoma:is the association explained solely by pigmentation phenotype? Am J Hum Genet 2000; 66:176-186.
16 Raimondi S, Sera F, Gandini S et al. MC1R variants, melanoma and red hair color phenotype:a meta-analysis. Int J Cancer 2008; 122:2753-2760.
17 Stratigos AJ, Dimisianos G, Nikolaou V et al. Melanocortin receptor-1 gene polymorphisms and the risk of cutaneous melanoma in a low-risk southern European population. J Invest Dermatol 2006; 126:1842-1849.
18 Valverde P. Healy E, Sikkink S et al. The Asp84Glu variant of the melanocortin 1 receptor (MC1R) is associated with melanoma. Hum Mol Genet 1996; 5: 1663-1666.
19 Gerstenblith MR, Goldstein AM, Fargnoli MC et al. Comprehensive evaluation of allele frequency differences of MC1R variants across populations. Hum Mutat 2007; 28:495-505.
20 Rees J. Plenty new under the sun. J Invest Dermatol 2006; 126:1691-1692.
21 Graf J, Hodgson R. van Daal A. Single nucleotide polymorphisms in the MATP gene are associated with normal human pigmentation variation. Hum Mutat 2005; 25:278-284.
22 Kanetsky PA, Swoyer J, Panossian S et al. A polymorphism in the agouti signaling protein gene is associated with human pigmentation. Am J Hum Genet 2002:70:770-775.
23 Lamason RL, Mohideen MA, Mest JR et al. SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans. Science 2005; 310: 1782-1786.
24 Norton HL, Kittles RA, Parra E et al. Genetic evidence for the convergent evolution of light skin in Europeans and East Asians. Mol Eiol Evol 2007; 24: 710-722.
25 Tomita Y, Suzuki T. Genetics of pigmentary disorders..Am J Med Genet C Semin Med Genet 2004; 131C:75-81.
26 Luande J, Henschke CI, Mohammed N. The Tanzanian human albino skin. Natural history. Cancer 1985; 55:1823-1828.
27 Perry PK, Silverberg NB. Cutaneous malignancy in albinism. Cutis 2001; 67: 427-430.
28 Terenziani M, Spreafico F, Serra A et al. Amelanotic melanoma in a child with oculocutaneous albinism. Med Pediatr Oncol 2003; 41:179-180.
29 Yakubu A, Mabogunje OA. Skin cancer in African albinos. Acta Oncol 1993; 32:621-622.
30 Fernandez LP, Milne RL, Pita G et al. SLC45A2:a novel malignant melanoma-associated gene. Hum Mutat 2008; 29:1161-1167.
31 Guedj M, Bourillon A, Combadieres C et al. Variants of the MATP/SLC45A2 gene are protective for melanoma in the French population. Hum Mutat 2008; 29:1154-1160.
32 Nakayama K, Fukamachi S, Kimura H et al. Distinctive distribution of AIM1 polymorphism among major human populations with different skin color. J Hum Genet 2002; 47:92-94.
33 Duffy DL, Zhao ZZ, Sturm RA et al. Multiple pigmentation gene polymorphisms account for a substantial proportion of risk of cutaneous malignant melanoma. J Invest Dermatol; 130:520-528.
34 Jannot AS, Meziani R, Bertrand G et al. Allele variations in the OCA2 gene (pink-eyed-dilution locus) are associated with genetic susceptibility to melanoma. Eur JH um Genet 2005; 13:913-920.
35 Bishop DT, Demenais F, Iies MM et al. Genome-wide association study identifies three loci associated with melanoma risk. Nat Genet 2009:41: 920-925.
36 Brown KM, Macgregor S, Montgomery GW et al. Common sequence variants on 20q11.22 confer melanoma susceptibility. Nat Genet 2008; 40:838-840.
37 Falchi M, Bataille V, Hayward NK et al. Genome-wide association study identifies variants at 9p21 and 22q13 associated with development of cutaneous nevi. Nat Genet 2009; 41:915-919.
38 Han J, Kraft P, Nan H et al. A genome-wide association study identifies novel alleles associated with hair color and skin pigmentation. PLoS Genet 2008; 4: e1000074.
39 Kayser M, Liu F, Janssens AC et al. Three genome-wide association studies and a linkage analysis identify HERC2 as a human iris color gene.Am J Hum Genet 2008;82:411-423.
40 Nan H, Kraft P, Qureshi AA et al. Genome-wide association study of tanning phenotype in a population of European ancestry. J Invest Dermatol 2009:129: 2250-2257.
41 Rafnar T, Sulem P, Stacey SN et al. Sequence variants at the TERT-CLPTM1L locus associate with many cancer types. Nat Genet 2009; 41:221-227.
42 Stacey SN, Gudbjartsson DF, Sulem P et al. Common variants on 1p36 and 1q42 are associated with cutaneous basal cell carcinoma but not with melanoma or pigmentation traits. Nat Genet 2008; 40:1313-1318.
43 Stacey SN, Sulem P, Masson G et al. New common variants affecting susceptibility to basal cell carcinoma. Nat Genet 2009; 41:909-914.
44 Stokowski RP, Pant PV, Dadd T et al. A genomewide association study of skin pigmentation in a South Asian population. Am J Hum Genet 2007; 81: 1119-1132.
45 Sulem P. Gudbjartsson DF, Stacey SN et al. Genetic determinants of hair, eye and skin pigmentation in Europeans. Nat Genet 2007; 39:1443-1452.
46 Sulem P, Gudbjartsson DF, Stacey SN et al. Two newly identified genetic determinants of pigmentation in Europeans. Nat Genet 2008; 40:835-837.
47 Jimbow K, Chen H, Park JS et al. Increased sensitivity of melanocytes to oxidative stress and abnormal expression of tyrosinase-related protein in vitiligo. Br J Dermatol 2001; 144:55-65.
48 Na GY, Lee KH, Kim MK et al. Polymorphisms in the melanocortin-1 receptor (MC1R) and agouti signaling protein (ASIP) genes in Korean vitiligo patients. Pigment Cell Res 2003; 16:383-387.
49 Szell M, Baltas E, Bodai L et al. The Arg160Trp allele of melanocortin-1 receptor gene might protect against vitiligo. Photochem Photobiol 2008; 84: 565-571.
50 Gathany AH, Hartge P, Davis S et al. Relationship between interferon regulatory factor 4 genetic polymorphisms, measures of sun sensitivity and risk for non-Hodgkin lymphoma. Cancer Causes Control 2009; 20:1291-1302.
51 Gudbjartsson DF, Sulem P, Stacey SN et al. ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinoma. Nat Genet 2008; 40:886-891.
52 Nan H, Kraft P, Hunter DJ et al. Genetic variants in pigmentation genes, pigmentary phenotypes, and risk of skin cancer in Caucasians. Int J Cancer 2009; 125:909-917.
53 Duffy DL, Montgomery GW, Chen W et al. A three-single-nucleotide polymorphism haplotype in intron 1 of OCA2 explains most human eye-color variation. Am J Hum Genet 2007; 80:241-252.
54 Fernandez LP, Milne RL, Pita G et al. Pigmentation-related genes and their implication in malignant melanoma susceptibility. Exp Dermatol 2009; 18: 634-642.
55 Lee YM, Ha MJ, Ryu MS et al. Assignments of the tyrosinase related protein-1 and-2 genes to human chromosome bands 9p23 and 13q32.1 by in situ hybridization. Yonsei Med J 2000; 41:398-400.
56 Manga P, Sato K, Ye L et al. Mutational analysis of the modulation of tyrosinase by tyrosinase-related proteins 1 and 2 in vitro. Pigment Cell Res 2000; 13:364-374.
57 Sarangarajan R, Zhao Y, Babcock G el al. Mutant alleles at the brown locus encoding tyrosinase-related protein-1 (TRP-1) affect proliferation of mouse melanocytes in culture. Pigment Cell Res 2000; 13:337-344.
58 Falchi M. Spector TD, Perks U et al. Genome-wide search for nevus density shows linkage to two melanoma loci on chromosome 9 and identifies a new QTL on 5q31 in an adult twin cohort. Hum Mol Genet 2006; 15:2975-2979.
59 Zhu G, Montgomery GW, James MR et al. A genome-wide scan for naevus count:linkage to CDKN2A and to other chromosome regions. Eur J Hum Genet 2007; 15:94-102.
60 Sundram U, Harvell JD, Rouse RV et al. Expression of the B-cell proliferation marker MUM1 by melanocytic lesions and comparison with S100, gp100 (HMB45), and MelanA. Mod Pathol 2003; 16:802-810.
61 Natkunam Y, Wamke RA, Montgomery K et al. Analysis of MUM1/IRF4 protein expression using tissue microarrays and immunohistochemistry. Mod Pathol 2001; 14:686-694.
62 Hultman KA, Bahary N, Zon LI et al. Gene Duplication of the zebrafish kit ligand and partitioning of melanocyte development functions to kit ligand a. PLoS Genet 2007; 3:e17.
63 Wehrle-Haller B. The role of Kit-ligand in melanocyte development and epidermal homeostasis. Pigment Cell Res 2003; 16:287-296.
64 Miller CT, Beleza S, Pollen AA et al. cis-Regulatory changes in Kit ligand expression and parallel evolution of pigmentation in sticklebacks and humans. Cell 2007; 131:1179-1189.
65 Wang Y, Broderick P, Webb E et al. Common 5p15.33 and 6p21.33 variants influence lung cancer risk. Nat Genet 2008; 40:1407-1409.
66 Eiberg H, Troelsen J, Nielsen M et al. Blue eye color in humans may be caused by a perfectly associated founder mutation in a regulatory element located within the HERC2 gene inhibiting OCA2 expression. Hum Genet 2008; 123: 177-187.
67 Sturm RA, Duffy DL, Zhao ZZ et al. A single SNP in an evolutionary conserved region within intron 86 of the HERC2 gene determines human blue-brown eye color. Am J Hum Genet 2008; 82:424-431.
68 Bahuau M, Vidaud D, Jenkins RB et al. Germ-line deletion involving the INK4 locus in familial proneness to melanoma and nervous system tumors. Cancer Res 1998; 58:2298-2303.
69 Borg A, Sandberg T, Nilsson K et al. High frequency of multiple melanomas and breast and pancreas carcinomas in CDKN2A mutation-positive melanoma families. J Natl Cancer Inst 2000; 92:1260-1266.
70 Hewitt C, Lee Wu C, Evans G et al. Germline mutation of ARF in a melanoma kindred. Hum Mol Genet 2002; 11:1273-1279.
71 Petronzelli F, Sollima D, Coppola G et al. CDKN2A germline splicing mutation affecting both p16(ink4) and p14(arf) RNA processing in a melanoma/neurofibroma kindred. Genes Chromosomes Cancer 2001; 31: 398-401.
72 Randerson-Moor JA, Harland M, Williams S et al. A germline deletion of p14(ARF) but not CDKN2A in a melanoma-neural system tumour syndrome family. Hum Mol Genet 2001; 10:55-62.
73 Rizos H, Puig S, Badenas C et al. A melanoma-associated germline mutation in exon 1 beta inactivates p14ARF. Oncogene 2001; 20:5543-5547.
74 Landi MT, Chatterjee N, Yu K et al. A genome-wide association study of lung cancer identifies a region of chromosome 5p15 associated with risk for adenocarcinoma. Am J Hum Genet 2009; 85:679-691.
75 Petersen GM, Amundadottir L, Fuchs CS et al. A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1 q32.1 and 5p15.33. Nat Genet; 42:224-228.
76 Shete S, Hosking FJ, Robertson LB et al. Genome-wide association study identifies five susceptibility loci for glioma. Nat Genet 2009; 41:899-904.
77 Han J, Qureshi AA, Prescott J et al. A prospective study of telomere length and the risk of skin cancer. J Invest Dermatol 2009; 129:415-421.
2 Zhang XJ, Chen JJ, Liu JB. The genetic concept of vitiligo. J Dermatol Sci 2005; 39:137-146.
3 Orozco-Topete R, Cordova-Lopez J, Yamamoto-Furusho JK et al. HLA-DRB1 *04 is associated with the genetic susceptibility to develop vitiligo in Mexican patients with autoimmune thyroid disease. J Am Acad Dermatol 2005; 52: 182-183.
4 Fain PR, Babu SR, Bennett DC et al. HLA class II haplotype DRB1*04-DQB1*0301 contributes to risk of familial generalized vitiligo and early disease onset. Pigment Cell Res 2006; 19:51-57.
5 Misri R, Khopkar U, Shankarkumar U et al. Comparative case control study of clinical features and human leukocyte antigen susceptibility between familial and nonfamilial vitiligo. Indian J Dermatol Venereol Leprol 2009; 75:583-587.
6 陈竺.医学遗传学.北京：人民卫生出版社.2001.
7 Risch N, Merikangas K. The future of genetic studies of complex human diseases. Science 1996; 273:1516-1517.
8 沈岩.人类疾病基因的识别——机遇与挑战.中国医学科学院学报 2005;27：263-264.
9 Lander ES, Linton LM, Birren B et al. Initial sequencing and analysis of the human genome. Nature 2001; 409:860-921.
10 Kruglyak L, Nickerson DA. Variation is the spice of life. Nat Genet 2001; 27: 234-236.
11 Sachidanandam R, Weissman D, Schmidt SC et al. A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature 2001; 409:928-933.
12 Quan C, Ren YQ, Xiang LH et al. Genome-wide association study for vitiligo identifies susceptibility loci at 6q27 and the MHC. Nat Genet; 42:614-618.
13 Zhang XJ, Huang W, Yang S et al. Psoriasis genome-wide association study identifies susceptibility variants within LCE gene cluster at 1q21. Nat Genet 2009; 41:205-210.
14 Han JW, Zheng HF, Cui Y et al. Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus. Nat Genet 2009; 41:1234-1237.
15 Zhang FR, Huang W, Chen SM et al. Genomewide association study of leprosy. NEngl J Med 2009; 361:2609-2618.
16 Wang LD, Zhou FY, Li XM et al. Genome-wide association study of esophageal squamous cell carcinoma in Chinese subjects identifies susceptibility loci at PLCE1 and C20orf54. Nat Genet,42:759-763.
17 Das SK. Majumder PP, Chakraborty R et al. Studies on vitiligo. I. Epidemiological profile in Calcutta, India. Genet Epidemiol 1985; 2:71-78.
18 Birlea SA, Fain PR, Spritz RA. A Romanian population isolate with high frequency of vitiligo and associated autoimmune diseases. Arch Dermatol 2008; 144:310-316.
19 Taieb A, Picardo M. Clinical practice. Vitiligo. N Engl J Med 2009; 360: 160-169.
20 Jacobson DL, Gange SJ, Rose NR et al. Epidemiology and estimated population burden of selected autoimmune diseases in the United States. Clin Immunol Immunopathol 1997; 84:223-243.
21 Mehta NR, Shah KC, Theodore C et al. Epidemiological study of vitiligo in Surat area, South Gujarat. Indian J Med Res 1973; 61:145-154.
22 Howitz J, Brodthagen H, Schwartz M et al. Prevalence of vitiligo. Epidemiological survey on the Isle of Bornholm. Denmark. Arch Dermatol 1977; 113:47-52.
23 Shajil EM, Chatterjee S, Agrawal D et al. Vitiligo:pathomechanisms and genetic polymorphism of susceptible genes. Indian J Exp Biol 2006; 44: 526-539.
24 Majumder PP. Genetics and prevalence of vitiligo vulgaris. In:Vitiligo (Harm SK, Nordlund JJ, eds). Oxford:Blackwell Science.2000; 18-20.
25 李凤岐,倪容之,蒋仲元.南京地区白癜风流行病学调查报告.中华皮肤科杂志 1987；20：332-333.
26 崔建,沈丽玉,王光超.450例白癜风临床分析.临床皮肤科杂志 1989；18：123-125.
27 孙廷泉,牛立军,刘涛.山东泰安地区白癜风流行病学调查报告.皮肤病与性病 1999；21：25-26.
28 徐元勇,叶冬青,童志才et al.安徽省宿州地区农村居民四种皮肤病流行病学调查.中华皮肤科杂志 2002；35：406-407.
29 Dogra S. Parsad D, Handa S et al. Late onset vitiligo:a study of 182 patients. M J Dermatol 2005; 44:193-196.
30 张学军.皮肤性病学,第6版edn.北京：人民卫生出版社.2004.
31 Hamm SK, Nordlund JJ. Vitiligo. Oxford:Blackwell Science.2000.
32 杨国亮,王侠生,eds.现代皮肤病学,1 edn.上海：上海医科大学出版社.1996.
33 Westerhof W, d'Ischia M. Vitiligo puzzle:the pieces fall in place. Pigment Cell Res 2007; 20:345-359.
34 Schallreuter KU, Bahadoran P, Picardo M et al. Vitiligo pathogenesis: autoimmune disease, genetic defect, excessive reactive oxygen species, calcium imbalance, or what else? Exp Dermatol 2008; 17:139-140; discussion 141-160.
35 Majumder PP, Das SK, Li CC. A genetical model for vitiligo. Am J Hum Genet 1988; 43:119-125.
36 Hafez M. Sharaf L, Abd el-Nabi SM. The genetics of vitiligo. Acta Derm Venereol 1983; 63:249-251.
37 Nath SK, Majumder PP, Nordlund JJ. Genetic epidemiology of vitiligo: multilocus recessivity cross-validated. Am J Hum Genet 1994; 55:981-990.
38 Zhang XJ, Liu JB, Gui JP et al. Characteristics of genetic epidemiology and genetic models for vitiligo. J Am Acad Dermatol 2004; 51:383-390.
39 Alkhateeb A, Fain PR, Thody A et al. Epidemiology of vitiligo and associated autoimmune diseases in Caucasian probands and their families. Pigment Cell Res 2003; 16:208-214.
40 Venkataram MN, White AG, Leeny WA et al. HLA antigens in Omani patients with vitiligo. Clin Exp Dermatol 1995; 20:35-37.
41 Majumder PP. Nordlund JJ, Nath SK. Pattern of familial aggregation of vitiligo. Arch Dermatol 1993; 129:994-998.
42 高天文,李强,李春英et al.白癜风2008例临床分析.中国皮肤性病学杂志 2002；16：304-306.
43 朱光斗.白癜风病因的初步探讨.临床皮肤科杂志 1990；19：9-11.
44 桂金萍,李玉珍,李进先et al.11080例白癜风患者及其家系分析.中华皮肤科杂志 2001：34：140.
45 马宏裕,倪修年,徐树平et al.1808例白癜风临床资料与分型研究.临床皮肤科杂志 2000；29：280-281.
46 孙越,韩菁,朱光斗.白癜风150例家系调查.临床皮肤科杂志 2000；29：149-150.
47 Spritz RA. The genetics of generalized vitiligo and associated autoimmune diseases. Pigment Cell Res 2007; 20:271-278.
48 Rezaei N, Gavalas NG, Weetman AP et al. Autoimmunity as an aetiological factor in vitiligo. J Eur Acad Dermatol Venereol 2007; 21:865-876.
49 Nath SK, Kelly JA, Namjou B et al. Evidence for a susceptibility gene, SLEV1, on chromosome 17p13 in families with vitiligo-related systemic lupus erythematosus. Am J Hum Genet 2001; 69:1401-1406.
50 Jin Y, Mailloux CM, Go wan K et al. NALP1 in vitiligo-associated multiple autoimmune disease. N Engl J Med 2007; 356:1216-1225.
51 Alkhateeb A, Stetler GL, Old W et al. Mapping of an autoimmunity susceptibility locus (AIS1) to chromosome 1p31.3-p32.2. Hum Mol Genet 2002; 11:661-667.
52 Alkhateeb A, Fain PR, Spritz RA. Candidate functional promoter variant in the FOXD3 melanoblast developmental regulator gene in autosomal dominant vitiligo. J Invest Dermatol 2005; 125:388-391.
53 Fain PR, Gowan K, LaBerge GS et al. A genomewide screen for generalized vitiligo:confirmation of AIS1 on chromosome 1p31 and evidence for additional susceptibility loci. Am J Hum Genet 2003; 72:1560-1564.
54 Spritz RA, Gowan K, Bennett DC et al. Novel vitiligo susceptibility loci on chromosomes 7 (AIS2) and 8 (AIS3), confirmation of SLEV1 on chromosome 17, and their roles in an autoimmune diathesis. Am J Hum Genet 2004:74: 188-191.
55 Horuk R, Yansura DG, Reilly D et al. Purification, receptor binding analysis, and biological characterization of human melanoma growth stimulating activity (MGSA). Evidence for a novel MGSA receptor. J Biol Chem 1993; 268: 541-546.
56 Her C, Aksoy IA, Kimura S et al. Human estrogen sulfotransferase gene (STE): cloning, structure, and chromosomal localization. Genomics 1995; 29:16-23.
57 Chen JJ, Huang W, Gui JP et al. A novel linkage to generalized vitiligo on 4q13-q21 identified in a genomewide linkage analysis of Chinese families. Am J Hum Genet 2005:76:1057-1065.
58 Liang Y. Yang S, Zhou Y et al. Evidence for two susceptibility loci on chromosomes 22q12 and 6p21-p22 in Chinese generalized vitiligo families. J Invest Dermatol 2007; 127:2552-2557.
59 Hirschhorn JN. Genomewide association studies--illuminating biologic pathways. N Engl J Med 2009; 360:1699-1701.
60 Donnelly P. Progress and challenges in genome-wide association studies in humans. Nature 2008; 456:728-731.
61 Birlea SA, Gowan K, Fain PR et al. Genome-wide association study of generalized vitiligo in an isolated European founder population identifies SMOC2, in close proximity to IDDM8. J Invest Dermatol 2009; 130:798-803.
62 肖毅,赵玉铭,宋芳吉et al. HLA-DRB1等位基因与中国北方汉族白癜风的相关性.中华皮肤科杂志 2000;33：5-7.
63 Tastan HB, Akar A, Orkunoglu FE et al. Association of HLA class I antigens and HLA class II alleles with vitiligo in a Turkish population. Pigment Cell Res 2004; 17:181-184.
64 Ren Y, Yang S, Xu S et al. Genetic variation of promoter sequence modulates XBP1 expression and genetic risk for vitiligo. PLoS Genet 2009; 5:e1000523.
65 Iacovelli P, Sinagra JL, Vidolin AP et al. Relevance of thyroiditis and of other autoimmune diseases in children with vitiligo. Dermatology 2005; 210:26-30.
66 Zhang Z, Xu SX, Zhang FY et al. The analysis of genetics and associated autoimmune diseases in Chinese vitiligo patients. Arch Dermatol Res 2009; 301: 167-173.
67 Le Poole IC, Wankowicz-Kalinska A, van den Wijngaard RM et al. Autoimmune aspects of depigmentation in vitiligo. J Investig Dermatol Symp Proc 2004: 9:68-72.
68 Park YK, Kim NS, Hann SK et al. Identification of autoantibody to melanocytes and characterization of vitiligo antigen in vitiligo patients. J Dermatol Sci 1996; 11:111-120.
69 Yee C, Thompson JA, Roche P et al. Melanocyte destruction after antigen-specific immunotherapy of melanoma:direct evidence of t cell-mediated vitiligo. J Exp Med 2000; 192:1637-1644.
70 Arcos-Burgos M, Parodi E, Salgar M et al. Vitiligo:complex segregation and linkage disequilibrium analyses with respect to microsatellite loci spanning the HLA. Hum Genet 2002; 110:334-342.
71 Schwartz DW, Felser B, Mayr WR. The genetics of HLA. Folia Biol (Praha) 1995; 41:123-139.
72 Helmuth R, Fildes N, Blake E et al. HLA-DQ alpha allele and genotype frequencies in various human populations, determined by using enzymatic amplification and oligonucleotide probes. Am J Hum Genet 1990; 47:515-523.
73 Gao X, Bhatia K, Trent RJ et al. HLA-DR,DQ nucleotide sequence polymorphisms in five Melanesian populations. Tissue Antigens 1992:40: 31-37.
74 Arnaiz-Villena A, Benmamar D, Alvarez M et al. HLA allele and haplotype frequencies in Algerians. Relatedness to Spaniards and Basques. Hum Immunol 1995; 43:259-268.
75 Zamani M, Spaepen M, Sghar SS et al. Linkage and association of HLA class Ⅱ genes with vitiligo in a Dutch population. Br J Dermatol 2001; 145:90-94.
76 A a-F, M a-A, F F. Study of HLA class Ⅰ/Ⅱ and T lymphocyte subsets in Kuwaiti vitiligo patients. Eur J Immunogenet 1995; 22:209-213.
77 Schallreuter KU, Levenig C, Kuhnl P et al. Histocompatibility antigens in vitiligo:Hamburg study on 102 patients from northern Germany. Dermatology 1993;187:186-192.
78 G O, L P, P M. Vitiligo is associated with a significant increase in HLA-A30, Cw6 and DQw3 and a decrease in C4AQ0 in northern Italian patients. Dermatology 1992; 185:123-127.
79 Buc M, Fazekasova H, Cechova E et al. Occurrence rates of HLA-DRB1, HLA-DQB1, and HLA-DPB1 alleles in patients suffering from vitiligo. Eur J Dermatol 1998; 8:13-15.
80 王珺赵,王岩,et al..北方汉族泛发型白癜风与HLA I 、 II类等位基因相关性研究.中华医学遗传学杂志 2007；24：221-223.
81 Liu JB, Li M, Chen H et al. Association of vitiligo with HLA-A2:a meta-analysis. J Eur Acad Dermatol Venereol 2007; 21:205-213.
82 Zhang XJ. Liu HS, Liang YH et al. Association of HLA class I alleles with vitiligo in Chinese Hans. J Dermatol Sci 2004; 35:165-168.
83 Yang S, Wang JY, Gao M et al. Association of HLA-DQA1 and DQB1 genes with vitiligo in Chinese Hans. Int J Dermatol 2005; 44:1022-1027.
84 Olerup O, Zetterquist H. HLA-DR typing by PCR amplification with sequence-specific primers (PCR-SSP) in 2 hours:an alternative to serological DR typing in clinical practice including donor-recipient matching in cadaveric transplantation. Tissue Antigens 1992; 39:225-235.
85 赵桐茂.骨髓库和脐血库中的HLA分型技术和策略.中国输血杂志 2001；14：382-385.
86 Taurog JD. The role of HLA-B27 in spondyloarthritis. J Rheumatol; 37: 2606-2616.
87 Thursz MR, Kwiatkowski D, Allsopp CE et al. Association between an MHC class II allele and clearance of hepatitis B virus in the Gambia. N Engl J Med 1995; 332:1065-1069.
88 Hill AV, Allsopp CE, Kwiatkowski D et al. Common west African HLA antigens are associated with protection from severe malaria. Nature 1991; 352: 595-600.
89 Thursz M, Yallop R, Goldin R et al. Influence of MHC class II genotype on outcome of infection with hepatitis C virus. The HENCORE group. Hepatitis C European Network for Cooperative Research. Lancet 1999; 354:2119-2124.
90 Dunstan SJ, Stephens HA, Blackwell JM et al. Genes of the class II and class III major histocompatibility complex are associated with typhoid fever in Vietnam. J Infect Dis 2001; 183:261-268.
91 Rossman MD, Thompson B, Frederick M et al. HLA-DRB1*1101:a significant risk factor for sarcoidosis in blacks and whites. Am J Hum Genet 2003:73:720-735.
92 Lang HL, Jacobsen H. Ikemizu S et al. A functional and structural basis for TCR cross-reactivity in multiple sclerosis. Nat Immunol 2002; 3:940-943.
93 Xiao Y ZY, Song FJ. Association of HLA-DRB1 alleles with generalized vitiligo in Chinese Hans in north China. Chinese J Dermatol 2000; 33:5-7.
94 Wang J, Zhao YM, Wang Y et al. Association of HLA class I and II alleles with generalized vitiligo in Chinese Hans in north China. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2007; 24:221-223.
95 Wang XY JR, Zhu MJ.. Association of HLA-DRB1 alleles with vitiligo and psoriasis vulgaris in Chinese Han people of Jilin region. Chinese J Immunol 2008; 28:144-146.
96 al Badri AM, Foulis AK, Todd PM et al. Abnormal expression of MHC class II and ICAM-1 by melanocytes in vitiligo. J Pathol 1993; 169:203-206.
97 Le Poole IC, van den Wijngaard RM, Westerhof W et al. Presence of T cells and macrophages in inflammatory vitiligo skin parallels melanocyte disappearance. Am J Pathol 1996; 148:1219-1228.
98 van den Wijngaard R. Wankowicz-Kalinska A, Le Poole C et al. Local immune response in skin of generalized vitiligo patients. Destruction of melanocytes is associated with the prominent presence of CLA+T cells at the perilesional site. Lab Invest 2000; 80:1299-1309.
99 Dawber RP. Vitiligo in mature-onset diabetes mellitus. Br J Dermatol 1968; 80: 275-278.
100 Sharma VK, Dawn G, Kumar B. Profile of alopecia areata in Northern India.Int J Dermatol 1996; 35:22-27.
101 Allison JR, Jr., Curtis AC. Vitiligo and pernicious anemia. AMA Arch Derm 1955; 72:407-408.
102 Dawber RP. Integumentary associations of pernicious anaemia. Br J Dermatol 1970; 82:221-223.
103 Grunnet I, Howitz J, Reymann F et al. Vitiligo and pernicious anemia. Arch Dermatol 1970; 101:82-85.
104 Koshiyama H, Ito M, Yoshinami N et al. Two cases of asymptomatic adrenocortical insufficiency with autoimmune thyroid disease. Endocr J 1994; 41:373-378.
105 Schallreuter KU, Lemke R, Brandt O et al. Vitiligo and other diseases: coexistence or true association? Hamburg study on 321 patients. Dermatology 1994; 188:269-275.
106 Kong MF, Jeffcoate W. Eighty-six cases of Addison's disease. Clin Endocrinol (Oxf) 1994; 41:757-761.
107 Meecham J, Jones EW. Addison's disease and Addisonian anaemia. Lancet 1967; 1:535-538.
108 Dunston GM, Halder RM. Vitiligo is associated with HLA-DR4 in black patients. A preliminary report. Arch Dermatol 1990; 126:56-60.
109 Zhang X, Wang H. Te-Shao H et al. The genetic epidemiology of psoriasis vulgaris in Chinese Han. Int J Dermatol 2002; 41:663-669.
1 Bale SJ, Dracopoli NC, Tucker MA et al. Mapping the gene for hereditary cutaneous malignant melanoma-dysplastic nevus to chromosome 1p. N Engl J Med 1989; 320:1367-1372.
2 Gillanders E, Juo SH, Holland EA et al. Localization of a novel melanoma susceptibility locus to 1p22. Am J Hum Genet 2003; 73:301-313.
3 Hussein MR, Roggero E, Tuthill RJ et al. Identification of novel deletion Loci at 1p36 and 9p22-21 in melanocytic dysplastic nevi and cutaneous malignant melanomas. Arch Dermatol 2003; 139:816-817.
4 Kefford RF,Newton Bishop JA, Bergman W et al. Counseling and DNA testing for individuals perceived to be genetically predisposed to melanoma:A consensus statement of the Melanoma Genetics Consortium. J Clin Oncol 1999: 17:3245-3251.
5 Goldstein AM, Chan M. Harland M et al. High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL. Cancer Res 2006; 66:9818-9828.
6 Epstein EH. Basal cell carcinomas:attack of the hedgehog. Nat Rev Cancer 2008; 8:743-754.
7 Rees JL. Genetics of hair and skin color. Annu Rev Genet 2003:37:67-90.
8 Rees JL. The genetics of sun sensitivity in humans. Am J Hum Genet 2004; 75: 739-751.
9 Bastiaens MT, ter Huurne JA, Kielich C et al. Melanocortin-1 receptor gene variants determine the risk of nonmelanoma skin cancer independently of fair skin and red hair. Am J Hum Genet 2001; 68:884-894.
10 Box NF, Duffy DL, Irving RE et al. Melanocortin-1 receptor genotype is a risk factor for basal and squamous cell carcinoma. J Invest Dermatol 2001:116: 224-229.
11 Kennedy C, ter Huurne J, Berkhout M et al. Melanocortin 1 receptor (MC1R) gene variants are associated with an increased risk for cutaneous melanoma which is largely independent of skin type and hair color. J Invest Dermatol 2001; 117:294-300.
12 Landi MT, Kanetsky PA, Tsang S et al. MC1R, ASIP, and DNA repair in sporadic and familial melanoma in a Mediterranean population. J Natl Cancer Inst 2005;97:998-1007.
13 Liboutet M, Portela M, Delestaing G et al. MC1R and PTCH gene polymorphism in French patients with basal cell carcinomas. J Invest Dermatol 2006: 126:1510-1517.
14 Matichard E, Verpillat P, Meziani R et al. Melanocortin 1 receptor (MC1R) gene variants may increase the risk of melanoma in France independently of clinical risk factors and UV exposure. J Med Genet 2004; 41:e13.
15 Palmer JS, Duffy DL, Box NF et al. Melanocortin-1 receptor polymorphisms and risk of melanoma:is the association explained solely by pigmentation phenotype? Am J Hum Genet 2000; 66:176-186.
16 Raimondi S, Sera F, Gandini S et al. MC1R variants, melanoma and red hair color phenotype:a meta-analysis. Int J Cancer 2008; 122:2753-2760.
17 Stratigos AJ, Dimisianos G, Nikolaou V et al. Melanocortin receptor-1 gene polymorphisms and the risk of cutaneous melanoma in a low-risk southern European population. J Invest Dermatol 2006; 126:1842-1849.
18 Valverde P. Healy E, Sikkink S et al. The Asp84Glu variant of the melanocortin 1 receptor (MC1R) is associated with melanoma. Hum Mol Genet 1996; 5: 1663-1666.
19 Gerstenblith MR, Goldstein AM, Fargnoli MC et al. Comprehensive evaluation of allele frequency differences of MC1R variants across populations. Hum Mutat 2007; 28:495-505.
20 Rees J. Plenty new under the sun. J Invest Dermatol 2006; 126:1691-1692.
21 Graf J, Hodgson R. van Daal A. Single nucleotide polymorphisms in the MATP gene are associated with normal human pigmentation variation. Hum Mutat 2005; 25:278-284.
22 Kanetsky PA, Swoyer J, Panossian S et al. A polymorphism in the agouti signaling protein gene is associated with human pigmentation. Am J Hum Genet 2002:70:770-775.
23 Lamason RL, Mohideen MA, Mest JR et al. SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans. Science 2005; 310: 1782-1786.
24 Norton HL, Kittles RA, Parra E et al. Genetic evidence for the convergent evolution of light skin in Europeans and East Asians. Mol Eiol Evol 2007; 24: 710-722.
25 Tomita Y, Suzuki T. Genetics of pigmentary disorders..Am J Med Genet C Semin Med Genet 2004; 131C:75-81.
26 Luande J, Henschke CI, Mohammed N. The Tanzanian human albino skin. Natural history. Cancer 1985; 55:1823-1828.
27 Perry PK, Silverberg NB. Cutaneous malignancy in albinism. Cutis 2001; 67: 427-430.
28 Terenziani M, Spreafico F, Serra A et al. Amelanotic melanoma in a child with oculocutaneous albinism. Med Pediatr Oncol 2003; 41:179-180.
29 Yakubu A, Mabogunje OA. Skin cancer in African albinos. Acta Oncol 1993; 32:621-622.
30 Fernandez LP, Milne RL, Pita G et al. SLC45A2:a novel malignant melanoma-associated gene. Hum Mutat 2008; 29:1161-1167.
31 Guedj M, Bourillon A, Combadieres C et al. Variants of the MATP/SLC45A2 gene are protective for melanoma in the French population. Hum Mutat 2008; 29:1154-1160.
32 Nakayama K, Fukamachi S, Kimura H et al. Distinctive distribution of AIM1 polymorphism among major human populations with different skin color. J Hum Genet 2002; 47:92-94.
33 Duffy DL, Zhao ZZ, Sturm RA et al. Multiple pigmentation gene polymorphisms account for a substantial proportion of risk of cutaneous malignant melanoma. J Invest Dermatol; 130:520-528.
34 Jannot AS, Meziani R, Bertrand G et al. Allele variations in the OCA2 gene (pink-eyed-dilution locus) are associated with genetic susceptibility to melanoma. Eur JH um Genet 2005; 13:913-920.
35 Bishop DT, Demenais F, Iies MM et al. Genome-wide association study identifies three loci associated with melanoma risk. Nat Genet 2009:41: 920-925.
36 Brown KM, Macgregor S, Montgomery GW et al. Common sequence variants on 20q11.22 confer melanoma susceptibility. Nat Genet 2008; 40:838-840.
37 Falchi M, Bataille V, Hayward NK et al. Genome-wide association study identifies variants at 9p21 and 22q13 associated with development of cutaneous nevi. Nat Genet 2009; 41:915-919.
38 Han J, Kraft P, Nan H et al. A genome-wide association study identifies novel alleles associated with hair color and skin pigmentation. PLoS Genet 2008; 4: e1000074.
39 Kayser M, Liu F, Janssens AC et al. Three genome-wide association studies and a linkage analysis identify HERC2 as a human iris color gene.Am J Hum Genet 2008;82:411-423.
40 Nan H, Kraft P, Qureshi AA et al. Genome-wide association study of tanning phenotype in a population of European ancestry. J Invest Dermatol 2009:129: 2250-2257.
41 Rafnar T, Sulem P, Stacey SN et al. Sequence variants at the TERT-CLPTM1L locus associate with many cancer types. Nat Genet 2009; 41:221-227.
42 Stacey SN, Gudbjartsson DF, Sulem P et al. Common variants on 1p36 and 1q42 are associated with cutaneous basal cell carcinoma but not with melanoma or pigmentation traits. Nat Genet 2008; 40:1313-1318.
43 Stacey SN, Sulem P, Masson G et al. New common variants affecting susceptibility to basal cell carcinoma. Nat Genet 2009; 41:909-914.
44 Stokowski RP, Pant PV, Dadd T et al. A genomewide association study of skin pigmentation in a South Asian population. Am J Hum Genet 2007; 81: 1119-1132.
45 Sulem P. Gudbjartsson DF, Stacey SN et al. Genetic determinants of hair, eye and skin pigmentation in Europeans. Nat Genet 2007; 39:1443-1452.
46 Sulem P, Gudbjartsson DF, Stacey SN et al. Two newly identified genetic determinants of pigmentation in Europeans. Nat Genet 2008; 40:835-837.
47 Jimbow K, Chen H, Park JS et al. Increased sensitivity of melanocytes to oxidative stress and abnormal expression of tyrosinase-related protein in vitiligo. Br J Dermatol 2001; 144:55-65.
48 Na GY, Lee KH, Kim MK et al. Polymorphisms in the melanocortin-1 receptor (MC1R) and agouti signaling protein (ASIP) genes in Korean vitiligo patients. Pigment Cell Res 2003; 16:383-387.
49 Szell M, Baltas E, Bodai L et al. The Arg160Trp allele of melanocortin-1 receptor gene might protect against vitiligo. Photochem Photobiol 2008; 84: 565-571.
50 Gathany AH, Hartge P, Davis S et al. Relationship between interferon regulatory factor 4 genetic polymorphisms, measures of sun sensitivity and risk for non-Hodgkin lymphoma. Cancer Causes Control 2009; 20:1291-1302.
51 Gudbjartsson DF, Sulem P, Stacey SN et al. ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinoma. Nat Genet 2008; 40:886-891.
52 Nan H, Kraft P, Hunter DJ et al. Genetic variants in pigmentation genes, pigmentary phenotypes, and risk of skin cancer in Caucasians. Int J Cancer 2009; 125:909-917.
53 Duffy DL, Montgomery GW, Chen W et al. A three-single-nucleotide polymorphism haplotype in intron 1 of OCA2 explains most human eye-color variation. Am J Hum Genet 2007; 80:241-252.
54 Fernandez LP, Milne RL, Pita G et al. Pigmentation-related genes and their implication in malignant melanoma susceptibility. Exp Dermatol 2009; 18: 634-642.
55 Lee YM, Ha MJ, Ryu MS et al. Assignments of the tyrosinase related protein-1 and-2 genes to human chromosome bands 9p23 and 13q32.1 by in situ hybridization. Yonsei Med J 2000; 41:398-400.
56 Manga P, Sato K, Ye L et al. Mutational analysis of the modulation of tyrosinase by tyrosinase-related proteins 1 and 2 in vitro. Pigment Cell Res 2000; 13:364-374.
57 Sarangarajan R, Zhao Y, Babcock G el al. Mutant alleles at the brown locus encoding tyrosinase-related protein-1 (TRP-1) affect proliferation of mouse melanocytes in culture. Pigment Cell Res 2000; 13:337-344.
58 Falchi M. Spector TD, Perks U et al. Genome-wide search for nevus density shows linkage to two melanoma loci on chromosome 9 and identifies a new QTL on 5q31 in an adult twin cohort. Hum Mol Genet 2006; 15:2975-2979.
59 Zhu G, Montgomery GW, James MR et al. A genome-wide scan for naevus count:linkage to CDKN2A and to other chromosome regions. Eur J Hum Genet 2007; 15:94-102.
60 Sundram U, Harvell JD, Rouse RV et al. Expression of the B-cell proliferation marker MUM1 by melanocytic lesions and comparison with S100, gp100 (HMB45), and MelanA. Mod Pathol 2003; 16:802-810.
61 Natkunam Y, Wamke RA, Montgomery K et al. Analysis of MUM1/IRF4 protein expression using tissue microarrays and immunohistochemistry. Mod Pathol 2001; 14:686-694.
62 Hultman KA, Bahary N, Zon LI et al. Gene Duplication of the zebrafish kit ligand and partitioning of melanocyte development functions to kit ligand a. PLoS Genet 2007; 3:e17.
63 Wehrle-Haller B. The role of Kit-ligand in melanocyte development and epidermal homeostasis. Pigment Cell Res 2003; 16:287-296.
64 Miller CT, Beleza S, Pollen AA et al. cis-Regulatory changes in Kit ligand expression and parallel evolution of pigmentation in sticklebacks and humans. Cell 2007; 131:1179-1189.
65 Wang Y, Broderick P, Webb E et al. Common 5p15.33 and 6p21.33 variants influence lung cancer risk. Nat Genet 2008; 40:1407-1409.
66 Eiberg H, Troelsen J, Nielsen M et al. Blue eye color in humans may be caused by a perfectly associated founder mutation in a regulatory element located within the HERC2 gene inhibiting OCA2 expression. Hum Genet 2008; 123: 177-187.
67 Sturm RA, Duffy DL, Zhao ZZ et al. A single SNP in an evolutionary conserved region within intron 86 of the HERC2 gene determines human blue-brown eye color. Am J Hum Genet 2008; 82:424-431.
68 Bahuau M, Vidaud D, Jenkins RB et al. Germ-line deletion involving the INK4 locus in familial proneness to melanoma and nervous system tumors. Cancer Res 1998; 58:2298-2303.
69 Borg A, Sandberg T, Nilsson K et al. High frequency of multiple melanomas and breast and pancreas carcinomas in CDKN2A mutation-positive melanoma families. J Natl Cancer Inst 2000; 92:1260-1266.
70 Hewitt C, Lee Wu C, Evans G et al. Germline mutation of ARF in a melanoma kindred. Hum Mol Genet 2002; 11:1273-1279.
71 Petronzelli F, Sollima D, Coppola G et al. CDKN2A germline splicing mutation affecting both p16(ink4) and p14(arf) RNA processing in a melanoma/neurofibroma kindred. Genes Chromosomes Cancer 2001; 31: 398-401.
72 Randerson-Moor JA, Harland M, Williams S et al. A germline deletion of p14(ARF) but not CDKN2A in a melanoma-neural system tumour syndrome family. Hum Mol Genet 2001; 10:55-62.
73 Rizos H, Puig S, Badenas C et al. A melanoma-associated germline mutation in exon 1 beta inactivates p14ARF. Oncogene 2001; 20:5543-5547.
74 Landi MT, Chatterjee N, Yu K et al. A genome-wide association study of lung cancer identifies a region of chromosome 5p15 associated with risk for adenocarcinoma. Am J Hum Genet 2009; 85:679-691.
75 Petersen GM, Amundadottir L, Fuchs CS et al. A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1 q32.1 and 5p15.33. Nat Genet; 42:224-228.
76 Shete S, Hosking FJ, Robertson LB et al. Genome-wide association study identifies five susceptibility loci for glioma. Nat Genet 2009; 41:899-904.
77 Han J, Qureshi AA, Prescott J et al. A prospective study of telomere length and the risk of skin cancer. J Invest Dermatol 2009; 129:415-421.
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