难治性慢性丙型肝炎中医证型与HLA-DP基因SNP的相关性研究
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摘要
目的探讨难治性慢性丙型肝炎(RCHC)中医证型与人类白细胞抗原(HLA)DP基因单核苷酸多态性(SNP)的相关性,寻找中医证型的分子标志物,为中医辨证提供科学依据。方法收集湖北省中医院收治的200例RCHC住院患者的一般临床资料、中医证型和肝功能指标[丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)、清蛋白(ALB)]、丙型肝炎病毒(HCV)RNA、HCV基因型、凝血酶原时间(PT)及血小板计数(PLT)检测结果;同时以100例该院其他科室收治的非RCHC患者为对照,采用双重荧光定量聚合酶链反应(FQ-PCR)技术对RCHC不同中医证型和对照组的HLA-DP基因rs9277535位点进行基因分型,统计分析各数据与中医证型的相关性。结果 200例RCHC中医证型中,肝郁脾虚证最多(100例,50.0%),然后依次是非肝郁脾虚型包括湿热内阻证(48例,24%)、肝肾阴虚证(32例,16.0%)和淤血阻络证(20例,10.0%);肝郁脾虚型与非肝郁脾虚型之间,年龄、肝功能指标和HCV基因型及HCV-RNA水平差异无统计学意义(P>0.05),但PT差异有统计学意义(P<0.05);与对照组相比,RCHC患者的肝郁脾虚组和非肝郁脾虚组的HLA-DP基因rs9277535基因型GG和AA分布差异均无统计学意义(P>0.05)。结论 HLADP基因rs9277535位点基因型GA杂合型和AA突变型在RCHC患者不同中医证型之间差异无统计学意义;但等位基因G和A的分布在肝郁脾虚组和非肝郁脾虚组有差异趋势,值得进一步研究。
Objective To investigate the correlation between syndrome types of traditional Chinese medicine(TCM)and HLA-DP gene polymorphisms in patients with refractory chronic hepatitis C(RCHC),and to find suitable molecular markers for TCM syndromes and provide scientific basis for TCM syndrome differentiation.Methods A total of 200 RCHC patients of Hubei Provincial Hospital of Traditional Chinese Medicine were enrolled retrospectively.Their general characteristics,TCM syndromes,data of liver function(ALT,AST,ALP and ALB),HCV RNA,HCV genotypes,PT and PLT were collected.At the same time,100 patients from other departments of the hospital were enrolled as control group.FQ-PCR was used to detect the genotypes of the HLA-DP gene rs9277535 sites of the RCHC patients with different TCM syndromes and the patients of control group.The correlation between the data and TCM syndromes was statistically analyzed.Results Among 200 patients in the study,the pattern of liver-depression and spleen-deficiency was maximum(100 cases,50.0%),while the remaining syndromes were dampness and heat resistance(48 cases,24.0%),yin deficiency of liver and kidney(32 cases,16.0%)and obstruction of collaterals by blood stasis(20 cases,10.0%).For age,data of liver function index and HCV RNA,there was no statistical difference between the liver-depression and spleen-deficiency type and other TCM syndromes(P>0.05).But the difference of PT was significant between liver-depression and spleen-deficiency type and other TCM syndromes(P<0.05).Compared with control group,there was no significant difference between the HLA-DP gene rs9277535 genotype GG and AA in the liver depression spleen deficiency group and the non-liver depression spleen deficiency group in the RCHC patients(P>0.05).Conclusion There was no significant difference between the genotypes of HLA-DP gene rs9277535 genotype GA heterozygous genes and AA homozygous genes in the different TCM syndromes of RCHC patients.However,the distribution of alleles G and A in liver depression spleen deficiency group and non-liver depression spleen deficiency group showed a different trend,which is worthy of further study.
Objective To investigate the correlation between syndrome types of traditional Chinese medicine(TCM)and HLA-DP gene polymorphisms in patients with refractory chronic hepatitis C(RCHC),and to find suitable molecular markers for TCM syndromes and provide scientific basis for TCM syndrome differentiation.Methods A total of 200 RCHC patients of Hubei Provincial Hospital of Traditional Chinese Medicine were enrolled retrospectively.Their general characteristics,TCM syndromes,data of liver function(ALT,AST,ALP and ALB),HCV RNA,HCV genotypes,PT and PLT were collected.At the same time,100 patients from other departments of the hospital were enrolled as control group.FQ-PCR was used to detect the genotypes of the HLA-DP gene rs9277535 sites of the RCHC patients with different TCM syndromes and the patients of control group.The correlation between the data and TCM syndromes was statistically analyzed.Results Among 200 patients in the study,the pattern of liver-depression and spleen-deficiency was maximum(100 cases,50.0%),while the remaining syndromes were dampness and heat resistance(48 cases,24.0%),yin deficiency of liver and kidney(32 cases,16.0%)and obstruction of collaterals by blood stasis(20 cases,10.0%).For age,data of liver function index and HCV RNA,there was no statistical difference between the liver-depression and spleen-deficiency type and other TCM syndromes(P>0.05).But the difference of PT was significant between liver-depression and spleen-deficiency type and other TCM syndromes(P<0.05).Compared with control group,there was no significant difference between the HLA-DP gene rs9277535 genotype GG and AA in the liver depression spleen deficiency group and the non-liver depression spleen deficiency group in the RCHC patients(P>0.05).Conclusion There was no significant difference between the genotypes of HLA-DP gene rs9277535 genotype GA heterozygous genes and AA homozygous genes in the different TCM syndromes of RCHC patients.However,the distribution of alleles G and A in liver depression spleen deficiency group and non-liver depression spleen deficiency group showed a different trend,which is worthy of further study.
引文
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[12]HUANG P,FAN H,TIAN T,et al.The relationship between human leukocyte antigen-DP/DQ gene polymorphisms and the outcomes of HCV infection in a Chinese population[J].Virol J,2017,14(1):235-241.
[2]薛博瑜.难治性慢性丙型肝炎的中医辨证论治[J].南京中医药大学学报,2015,31(1):1-3.
[3]王成宝,陈逸云,聂红明,等.基于循证医学的慢性丙型肝炎患者病毒基因分型与中医证候之间的关系探讨[J].中西医结合肝病杂志,2014,24(5):259-261.
[4]中华医学会肝病学分会.丙型肝炎防治指南(2015更新版)[J].肝脏,2015,33(12):933-949.
[5]中华中医药学会肝胆病分会.病毒性肝炎中医辨证标准(2017年版)[J].中西医结合肝病杂志,2017,27(3):193-194.
[6]谢尧,李明慧.难治性丙型肝炎治疗现状及发展趋势[J].中华肝脏病杂志,2009,17(7):484-486.
[7]陈新月,尚佳,杨瑞锋.难治性慢性丙型肝炎初治患者优先治疗后的病毒学应答率研究[J].中华肝脏病杂志,2015,23(6):412-417.
[8] FRIED M W,JENSEN D M,RODRIGUEZ-TORRES M,et al.Improved outcomes in patients hepatitis C with difficult-to-treat characteristics:randomized study of higher doses of peginterferon alpha-2aan ribavirin[J].Hepatology,2008,48(4):1033-1043.
[9]冯晓霞,聂苑霞,梁海林.益气解毒化瘀方联合抗病毒治疗对难治性慢性丙型肝炎患者外周血淋巴细胞亚群和炎性细胞因子的影响[J].实用肝脏病杂志,2016(6):674-677.
[10]沈健,陈建杰,商斌仪,等.丙肝冲剂治疗难治性丙型肝炎研究[J].现代中西医结合杂志,2013,22(18):1947-1949.
[11]刘娟娟.HLA-DP多态性与乙型肝炎病毒感染及其不同结局相关性Meta分析[D].昆明:昆明医科大学,2017.
[12]HUANG P,FAN H,TIAN T,et al.The relationship between human leukocyte antigen-DP/DQ gene polymorphisms and the outcomes of HCV infection in a Chinese population[J].Virol J,2017,14(1):235-241.