VKDC/VKOR在草酸钙尿石形成过程中的作用及分子机制的初探
|
摘要
第一部分维生素K依赖性羧化酶(VKDC)在草酸钙尿石症患者肾组织中活性及表达的研究
目的对草酸钙尿石症患者肾组织中维生素K依赖性羧化酶(VKDC or GGCX)的活性及表达进行检测，探讨其与草酸钙尿石形成的关系。
方法收集肾脏皮质组织标本71例，其中草酸钙尿石组44例，对照组27例(肾盂输尿管交界处狭窄和输尿管结核组6例，肾肿瘤皮质组21例)。采用超速离心提取羧化酶，运用同位素标记的羧化反应检测尿石症患者肾组织VKDC活性：应用免疫组织化学法确定VKDC在肾脏皮质组织中的表达部位，应用免疫印迹(Western blot)蛋白半定量法，检测各组VKDC蛋白的表达。
结果草酸钙尿石症患者肾组织中VKDC活性显著低于对照组。VKDC在结石组和对照组中均有表达，主要位于肾皮质肾小管上皮细胞的胞浆，但在尿石组中的表达(27．64±0．29)明显低于对照组(53．78±0．33、55．22±0．36)，差异有统计学意义(P＜0．05)。
结论VKDC在草酸钙尿石症患者肾组织的活性和表达均降低，这些改变可能与草酸钙尿石的形成有关。
第二部分草酸钙尿石症患者肾组织γ-羧基谷氨酸羧化酶(GGCX)基因3’-非翻译区(3’-UTR)变异的初步研究
目的探讨γ-羧基谷氨酸羧化酶(GGCX)基因3’-非翻译区(3’-untranslated region，3’-UTR)的分子变异及与草酸钙尿石症的关系。
方法收集肾脏皮质组织标本，其中草酸钙尿石组42例，对照组31例(非尿石组及肾肿瘤组)，提取肾脏组织RNA后采用快速cDNA末端扩增(RACE)技术扩增GGCX基因的3’-UTR，将扩增的特异带回收纯化，构建到原核表达载体中，提取质粒后进行酶切鉴定，并测序后与NCBI核酸数据库进行比对。
结果GGCX基因第一次套式PCR扩增未见明显特异带，2次套式PCR结果可见约1000bp特异带，回收后连接到pGEM-T中，转化到大肠杆菌中并少选阳性菌落，提取质粒进行酶切鉴定后测序，于NCBI核酸数据库进行比对，结果未发现该段序列存在插入或缺失。
结论草酸钙尿石患者VKDC表达下调可能与γ-羧基谷氨酸羧化酶(GGCX)基因的3’非翻译区无明显相关。
第三部分维生素K环氧化物还原酶亚单位1(VKORC1)在草酸钙尿石症患者肾组织中的表达及意义
目的探讨草酸钙尿石症患者肾组织中维生素K坏氧化物还原酶亚单位1(VKORC1)的表达及意义。
方法收集肾脏皮质组织标本71例，其中草酸钙结石组44例，对照组27例(肾盂输尿管交界处狭窄和输尿管结核组6例，皮质厚度小于1．0cm；肾肿瘤皮质组21例，皮质厚度大于1．0cm)，应用免疫组织化学法检测VKORC1在组织中的表达部位，应用免疫印迹(Western blot)蛋白半定量法，检测各组VKORC1蛋白的表达，并分析其表达与肾脏积水及皮质厚度等因素的关系。
结果VKORC1定位于肾皮质肾小管上皮细胞的胞浆。对照组间VKORC1的表达(262．16±7．33和286．71±9．82)无明显差异，P＞0．05，但结石组VKORC1蛋白的表达(122．33±11．34)明显低于对照组，差异有统计学意义(P＜0．05)。
结论草酸钙尿石症患者肾组织内VKORC1表达降低在草酸钙尿石形成中有重要作用，并可能通过维生素K循环作用于VKDC而发挥机制。
PartⅠActivity and expression of vitamin K dependentgamma-glutamyl carboxylase in patients with calcium oxalateurolithiasis
Objectives To explore the activity and expression of vitamin K dependentgamma-glutamyl carboxylase (GGCX or VKDC) in patients with calcium oxalateurolithiasis and evaluate the correlation between the VKDC and the formation of calciumoxalate calculus.
Methods Specimens of renal tissues were harvested from urolithic patients, controltissues were obtained from renal tumor patients performing nephrectomy and non-urolithicpatients. The carboxylase activity was detected by the isotope labeled carboxylatic reactionin vitro and immunohistochemical technique was established to study the location ofVKDC in renal tissues. We also detected the differential expression of VKDC in renaltissues in surgical tissue specimens with Western blot.
Results VKDC was located in the cytoplasm of renal tubular epithelial cell and theactivity in urolithic group was significantly decreased compared with that of controls(P＜0.05). The expression of protein in urolithic group (27.64±0.29) was weaker than theother two control groups (55.22±0.36 and 53.78±0.33), P＜0.05.
Conclusions The activity and expression of VKDC are decreased in renal tissues of patients with calcium oxalate urolithiasis, and VKDC may be involved in the formation ofcalcium oxalate calculus.
PartⅡVariation of gamma-glutamyl carboxylase gene3'-untranslated region in patients with urolithiasis
Objectives: To get the 3'-untranslated region of gamma-glutamyl carboxylase (GGCX)gene and analyze the relationship between 3'UTR of GGCX and urolithiasis.
Methods: Specimens of renal tissues were harvested from urolithic patients, controltissues were obtained from renal tumor patients performing nephrectomy and non-urolithicpatients. The 3'UTR of GGCX sequence was amplified by rapid amplification of cDNAends (RACE). The fragment was purified to construct the corresponding recombinantplasid, subsequently the plasid was sequenced to analyse and BLAST with NCBInucleotide data bank.
Results: Although the specific fragments were not quite clear after the first nestedPCR reaction, about 1000 bp fragment was obtained in second nested PCR amplification,and inserted into pGEM-T vector. The recombinant plasmid was transformed into JM 109cells, and then sequenced. We didn't find insertion or deletion in this region.
Conclusions: We succeed to clone the 3'UTR sequence of GGCX by RACE. but wecouldn't conclude that there are some relationship between 3'UTR of GGCX andurolithiasis.
PartⅢThe expression of vitamin K epoxide reductase complexsubunit 1 (VKORC1) in patients with urolithiasis
Objective: To stud the expression of vitamin K epoxide reductase complex subunit 1(VKORC1) in patients with urolithiasis and evaluate the correlation between the quantityof VKORC1 and the formation of calcium oxalate calculus.
Methods: Forty-four specimens of renal tissues were harvested from urolithic patients,control tissues were harvested from non-urolithic patients (6 specimens) and renal tumorpatients performing nephrectomy (21 specimens). Immunohistochemical technique wasestablished to study the location of VKORC1 in renal tissues. Western blot technique wasused to detect the differential expression of VKORC1 protein in renal tissues.
Results: VKORC1 protein located in the cytoplasm of renal tubular epithelial cell.The protein expression of VKORC1 in urolithic group (122.33±11.34) was weaker than theother two control groups (262.16±7.33 and 286.71±9.82), P＜0.05.
Conclusion: The low expression reductase in the calcium oxalate urolithic patientsmay play an important role by vitamin K circle in the formation of calcium oxalateurolithiasis.
目的对草酸钙尿石症患者肾组织中维生素K依赖性羧化酶(VKDC or GGCX)的活性及表达进行检测，探讨其与草酸钙尿石形成的关系。
方法收集肾脏皮质组织标本71例，其中草酸钙尿石组44例，对照组27例(肾盂输尿管交界处狭窄和输尿管结核组6例，肾肿瘤皮质组21例)。采用超速离心提取羧化酶，运用同位素标记的羧化反应检测尿石症患者肾组织VKDC活性：应用免疫组织化学法确定VKDC在肾脏皮质组织中的表达部位，应用免疫印迹(Western blot)蛋白半定量法，检测各组VKDC蛋白的表达。
结果草酸钙尿石症患者肾组织中VKDC活性显著低于对照组。VKDC在结石组和对照组中均有表达，主要位于肾皮质肾小管上皮细胞的胞浆，但在尿石组中的表达(27．64±0．29)明显低于对照组(53．78±0．33、55．22±0．36)，差异有统计学意义(P＜0．05)。
结论VKDC在草酸钙尿石症患者肾组织的活性和表达均降低，这些改变可能与草酸钙尿石的形成有关。
第二部分草酸钙尿石症患者肾组织γ-羧基谷氨酸羧化酶(GGCX)基因3’-非翻译区(3’-UTR)变异的初步研究
目的探讨γ-羧基谷氨酸羧化酶(GGCX)基因3’-非翻译区(3’-untranslated region，3’-UTR)的分子变异及与草酸钙尿石症的关系。
方法收集肾脏皮质组织标本，其中草酸钙尿石组42例，对照组31例(非尿石组及肾肿瘤组)，提取肾脏组织RNA后采用快速cDNA末端扩增(RACE)技术扩增GGCX基因的3’-UTR，将扩增的特异带回收纯化，构建到原核表达载体中，提取质粒后进行酶切鉴定，并测序后与NCBI核酸数据库进行比对。
结果GGCX基因第一次套式PCR扩增未见明显特异带，2次套式PCR结果可见约1000bp特异带，回收后连接到pGEM-T中，转化到大肠杆菌中并少选阳性菌落，提取质粒进行酶切鉴定后测序，于NCBI核酸数据库进行比对，结果未发现该段序列存在插入或缺失。
结论草酸钙尿石患者VKDC表达下调可能与γ-羧基谷氨酸羧化酶(GGCX)基因的3’非翻译区无明显相关。
第三部分维生素K环氧化物还原酶亚单位1(VKORC1)在草酸钙尿石症患者肾组织中的表达及意义
目的探讨草酸钙尿石症患者肾组织中维生素K坏氧化物还原酶亚单位1(VKORC1)的表达及意义。
方法收集肾脏皮质组织标本71例，其中草酸钙结石组44例，对照组27例(肾盂输尿管交界处狭窄和输尿管结核组6例，皮质厚度小于1．0cm；肾肿瘤皮质组21例，皮质厚度大于1．0cm)，应用免疫组织化学法检测VKORC1在组织中的表达部位，应用免疫印迹(Western blot)蛋白半定量法，检测各组VKORC1蛋白的表达，并分析其表达与肾脏积水及皮质厚度等因素的关系。
结果VKORC1定位于肾皮质肾小管上皮细胞的胞浆。对照组间VKORC1的表达(262．16±7．33和286．71±9．82)无明显差异，P＞0．05，但结石组VKORC1蛋白的表达(122．33±11．34)明显低于对照组，差异有统计学意义(P＜0．05)。
结论草酸钙尿石症患者肾组织内VKORC1表达降低在草酸钙尿石形成中有重要作用，并可能通过维生素K循环作用于VKDC而发挥机制。
PartⅠActivity and expression of vitamin K dependentgamma-glutamyl carboxylase in patients with calcium oxalateurolithiasis
Objectives To explore the activity and expression of vitamin K dependentgamma-glutamyl carboxylase (GGCX or VKDC) in patients with calcium oxalateurolithiasis and evaluate the correlation between the VKDC and the formation of calciumoxalate calculus.
Methods Specimens of renal tissues were harvested from urolithic patients, controltissues were obtained from renal tumor patients performing nephrectomy and non-urolithicpatients. The carboxylase activity was detected by the isotope labeled carboxylatic reactionin vitro and immunohistochemical technique was established to study the location ofVKDC in renal tissues. We also detected the differential expression of VKDC in renaltissues in surgical tissue specimens with Western blot.
Results VKDC was located in the cytoplasm of renal tubular epithelial cell and theactivity in urolithic group was significantly decreased compared with that of controls(P＜0.05). The expression of protein in urolithic group (27.64±0.29) was weaker than theother two control groups (55.22±0.36 and 53.78±0.33), P＜0.05.
Conclusions The activity and expression of VKDC are decreased in renal tissues of patients with calcium oxalate urolithiasis, and VKDC may be involved in the formation ofcalcium oxalate calculus.
PartⅡVariation of gamma-glutamyl carboxylase gene3'-untranslated region in patients with urolithiasis
Objectives: To get the 3'-untranslated region of gamma-glutamyl carboxylase (GGCX)gene and analyze the relationship between 3'UTR of GGCX and urolithiasis.
Methods: Specimens of renal tissues were harvested from urolithic patients, controltissues were obtained from renal tumor patients performing nephrectomy and non-urolithicpatients. The 3'UTR of GGCX sequence was amplified by rapid amplification of cDNAends (RACE). The fragment was purified to construct the corresponding recombinantplasid, subsequently the plasid was sequenced to analyse and BLAST with NCBInucleotide data bank.
Results: Although the specific fragments were not quite clear after the first nestedPCR reaction, about 1000 bp fragment was obtained in second nested PCR amplification,and inserted into pGEM-T vector. The recombinant plasmid was transformed into JM 109cells, and then sequenced. We didn't find insertion or deletion in this region.
Conclusions: We succeed to clone the 3'UTR sequence of GGCX by RACE. but wecouldn't conclude that there are some relationship between 3'UTR of GGCX andurolithiasis.
PartⅢThe expression of vitamin K epoxide reductase complexsubunit 1 (VKORC1) in patients with urolithiasis
Objective: To stud the expression of vitamin K epoxide reductase complex subunit 1(VKORC1) in patients with urolithiasis and evaluate the correlation between the quantityof VKORC1 and the formation of calcium oxalate calculus.
Methods: Forty-four specimens of renal tissues were harvested from urolithic patients,control tissues were harvested from non-urolithic patients (6 specimens) and renal tumorpatients performing nephrectomy (21 specimens). Immunohistochemical technique wasestablished to study the location of VKORC1 in renal tissues. Western blot technique wasused to detect the differential expression of VKORC1 protein in renal tissues.
Results: VKORC1 protein located in the cytoplasm of renal tubular epithelial cell.The protein expression of VKORC1 in urolithic group (122.33±11.34) was weaker than theother two control groups (262.16±7.33 and 286.71±9.82), P＜0.05.
Conclusion: The low expression reductase in the calcium oxalate urolithic patientsmay play an important role by vitamin K circle in the formation of calcium oxalateurolithiasis.
引文
1．叶章群．泌尿系结石研究现况与展望．中华实验外科杂志，2005，22：261-262．
2. MJ Stechman, NY Loh, RV Thakker. Genetics of hypercalciuric nephrolithiasis: renal stone disease. Annals of the New York Academy of Sciences, 2007, 1116:461-467.
3．朱绍兴，章咏裳，刘继红．晶体表面结合蛋白对草酸钙晶体生长的抑制作用．中华泌尿外科杂志，1998，19(8)：457-459．
4. Liu J, Wang T, Chen J, et al. Decreased inhibitory activity of prothrombin to calcium oxalate crystallization by specific chemical modification of its γ-carboxyglutamic acid residues. Urology, 2006, 67:201-203.
5. Grover PK, Miyazawa K, Coleman M, et al. Renal prothrombin mRNAis significantly decreased in a hyperoxaluric rat model of nephrolithiasis. J Pathol, 2006, 210:273-276.
6. Liu J, Chen J, Wang T, et al. Effects of urinary prothrombin fragment lin the formation of calcium oxalate calculus. J Urol, 2005, 173:113-116.
7. Bing Gao, Takahiro Yasui, Yasunori Itoh, et al. A polymorphism of matrix Gla protein gene is associated with kidney stones. J Urol, 2007, 177:2361-2365.
8. Kathleen L. Berkner. The vitamin K-dependent caroxylase. Annual Review of Nutrition, 2005, 25:127-149.
9. Tao Li, Chun-Yun Chang, Da-Yun Jin, et al. Identification of the gene for vitamin K epoxide reductase. Nature, 2004, 427:541-544.
10. Jian-Ke, Tie, Christopher Nicchitta, Gunnar von Heijne, et al. Membrane Topology Mapping of Vitamin K Epoxide Reductase by in Vitro Translation/Co translocation. J. Biol. Chem, 2005, 280:16410-16415.
11. Anderea A, Garcia, Pieter H. Reitsma. VKORC1 and the Vitamin K Cycle. In: Gerald, eds. Vitamin K and hormons Volum 78. London: Academic, 2008.23
12. Simone R, Andreas Fregin, Vytautas Ivaskevicius, et al. Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature, 2004, 427:537-541.
13. Chen JH, Liu JH, Zhang YS, et al. Decreased renal vitamin K-dependent gamma-glutamyl carboxylase activity in calcium oxalate calculi patients. Chin Med J (Engl),2003, 116:569-571.
1. Saeed R Khan, Dirk J. Modulators of urinary stone formation. Fornt Biosci, 2004, 9:1450-1482.
2. Liu J, Chen J, Wang T, et al. Effects of urinary prothrombin fragment lin the formation of calcium oxalate calculus. J Urol, 2005, 173:113-116.
3. Chen JH, Liu JH, Zhang YS, et al. Decreased renal vitamin K-dependent gamma-glutamyl carboxylase activity in calcium oxalate calculi patients. Chin Med J (Engl), 2003, 116:569-571.
4. Gary M. Wood, J. W. Suttie. Vitamin K-dependent Carboxylase. J Biol Chem. 1988, 263:3234-3239.
5. Liu J, Wang T, Chen J, et al. Decreased inhibitory activity of prothrombin to calcium oxalate crystallization by specific chemical modification of its γ-carboxyglutamic acid residues. Urology, 2006, 67:201-203.
6. Stapleton AMF, Timme TL, Ryall RL. The gene expression ofprothombin in the human kidney: its potential relevance to kidney stone disease. Bri J Urol, 1998; 61:666-668.
7. Bing Gao, Takahiro Yasui, Yasunori Itoh, et al. A polymorphism of matrix Gla protein gene is associated with kidney stones. J Urol, 2007, 177:2361-2365.
8．王少刚，刘继红，章咏裳．草酸钙结石患者尿中蛋白结合型γ-羧基谷氨酸的检测意义．中华泌尿外科杂志，2002，23：428-430．
9. Furie B, Bouchard BA, Furie BC. Vitamin K-dependent biosynthesis of γ-carboxy-glutamic acid. Blood, 1999, 93:1798-1808.
10. Kumar V, Farell G, Lieske JC. Whole urinary proteins coat calcium oxalate monohydrate crystals to greatly decrease their adhesion to renal cells. J Urol. 2003, 170:221-225.
11. Friedman PA, Mitch WE, Silva P. Localization of renal vitamin K-dependent gamma-glutamyl carboxylase to tubule cells. J Biol Chem 1982, 257:11037-11044.
12. Berkner KL, McNally BA. Purification of vitamin K-dependent carboxylase from cultured cells. Methods Enzymol, 1997;282:313-333
13. Angayarkanni N, Selvam R, Enhanced renal vitamin-K-dependent gamma- glutarnyl carboxylase activity in experimental rat urolithiasis. Eur Urol, 1998, 33:116-120.
14．杨俊，刘继红，郭小林，等．草酸钙尿石症患者肾组织VKDC基因表达及其意义．临床泌尿外科杂志，2007，22：736-738．
15. Wadelius M, Chen LY, Downes K, et al. Common VKORC1 and GGCX polymorphisms associated with warfarin dose. Pharmacogenomics J, 2005, 5:262-270.
16．龚小新，刘继红，郭小林，等．草酸钙尿石患者VKDC结构域基因突变的研究．中华实验外科杂志，2007，24：1606-1607．
17. Chen DH, Kaung HL, Miller CM, et al: Microarray analysis of changes in renal phenotype in the ethylene glycol rat model of urolithiasis: potential and pitfalls. BJU Int, 2004, 94:637-650.
18. Grover PK, Miyazawa K, Coleman M, et al: Renal prothrombin mRNA is significantly decreased in a hyperoxaluric rat model of nephrolithiasis. J Pathol, 2006, 210:273-281.
1. Stafford DW. The vitamin K cycle [J]. J Thromb Haemost. 2005; 3(8):1873-1878.
2. Romero EE, Marvi U, Niman ZE, et al. The vitamin K-dependent gamma-glutamyl carboxylase gene contains a TATA-less promoter with a novel upstream regulatory element [J].Blood. 2003; 102(4):1333-1339.
3. Romero EE, Velazquez-Estades LJ, Deo R, et al. Cloning of rat vitamin K-dependent gamma-glutamyl carboxylase and developmentally regulated gene expression in postimplantation embryos [J]. Exp Cell Res. 1998; 243(2):334-346.
4．杨俊，刘继红，郭小林，等．草酸钙尿石症患者肾组织VKDC基因表达的研究[J]．临床泌尿外科杂志．2007；22(10)：736-738．
5．王少刚，刘继红，章咏裳．草酸钙结石患者尿中蛋白结合型γ-羧基谷氨酸的检测意义[J]．中华泌尿外科杂志．2002；23(7)：428-430．
6．陈俊汇，刘继红，章咏裳，等．草酸钙尿结石患者肾组织维生素K依赖羧化酶活性的研究[J]．中华泌尿外科杂志．2002；23(12)：725-727．
7. Chen Z, Kai G, Liu X, et al. cDNA cloning and characterization of a mannose-binding lectin from Zingiber officinale Roscoe rhizomes. J Biosci. 2005, 30:213-220.
8. Chung Moh M, Hoon Lee L, Shen S. Cloning and characterization of hepaCAM a novel Ig-like cell adhesion molecule suppressed in human hepatocellular carcinoma. J Hepatol. 2005,42:833-841.
9．张陆，惠汝太．3’非翻译区在转录后调控中的作用．中国分子心脏病学杂志，2005，5：619-624．
10. Lorenzo Malquori, Laura Carsetti, Giovina Ruberti. The 3'-UTR of the human CTLA4 mRNA stability and translational efficiency. Bioch. Biop. Acta. 2007,10:1111-1116.
11. Flavio Mignone, Carmela Gissi, Sabino Liuni, et al. Umtranslated regions of mRNAs. Genome Biology. 2002, 3:0004.1-0004.10.
12. Shi Tongdong, Wu Yuzhang, Zhu Xihua. 3'-Untranslated region of eukaryotic mRNA in gene regulation. Prog Biochem Biophys, 1998, 25:195-197.
13. Romero EE, Velazquez-Estades LJ, Deo R, et al. Cloning of rat vitamin K-dependent gamma-glutamy] carboxylase and developmentally regulated gene expression in postimplantation embryos [J]. Exp Cell Res. 1998, 243(2):334-346.
14. Prezioso D, Di Martino M, Galasso R, et al. Laboratory assessment [J]. Urol Int. 2007,79 Suppl 1:20-25.
1. Saeed R Khan, Dirk J. Modulators of urinary stone formation, 2004, 9:1450-1452.
2． 叶章群．泌尿系结石研究现况与展望．中华实验外科杂志，2005，22：261-262．
3. Kathleen L. Berkner. The vitamin K-dependent caroxylase. Annual Review of Nutrition, 2005, 25:127-149.
4. Anderea A, Garcia, Pieter H. Reitsma. VKORC1 and the Vitamin K Cycle. In: Gerald, eds. Vitamin K and hormons Volum 78. London: Academic, 2008.23
5. Tao Li, Chun-Yun Chang, Da-Yun Jin, et al. Identification of the gene for vitamin K epoxide reductase. Nature, 2004, 427:541-546.
6. Jian-Ke, Tie, Christopher Nicchitta, Gunnar von Heijne, et al. Membrane Topology Mapping of Vitamin K Epoxide Reductase by in Vitro Translation/Co translocation. J. Biol. Chem, 2005, 280:16410-16415.
7. Oldenburg J, Marinova M, Muller C., et al. The Vitamin K circle. Vitam Horm, 2008, 78: 35-62.
8. D. Darghouth, KW. Hallgren, RL. Shtofrnan, et al. Compound heterozygosity of novel missense mutations in the gamma-glutamylcarboxylase gene causes hereditary combined vitamin K-dependent coagulation factor deficiency. Blood, 2006, 108:1925-1931.
9. Nadeem Wajih, David C. Sane, Susan M. Huston, et al. Engineering of a recombinant vitamin K-dependent gamma-carboxylation system with enhanced gamma-carboxy-glutamic acid forming capacity. J. Biol. Chem, 2005, 280:10540-10547.
10. MJ Stechman, NY Loh, RV Thakker. Genetics of hypercalciuric nephrolithiasis: renal stone disease. Annals of the New York Academy of Sciences, 2007, 1116:461
11．朱绍兴，章咏裳，刘继红．晶体表面结合蛋白对草酸钙晶体生长的抑制作用．中华泌尿外科杂志，1998，19(8)：457-459．
12. Liu J, Wang T, Chen J, et al. Decreased inhibitory activity of prothrombin to calcium oxalate crystallization by specific chemical modification of its y-carboxyglutamic acid residues. Urology, 2006, 67:201-203.
13. Grover PK, Miyazawa K, Coleman M, et al. Renal prothrombin mRNAis significantly decreased in a hyperoxaluric rat model of nephrolithiasis. J Pathol, 2006, 210:273-276.
14. Liu JH, Chen JH, Wang T, et al. Effects of urinary prothrombin fragment 1 in the formation of calcium oxalate calculus. J Urol, 2005,173:113-116
15. Bing Gao, Takahiro Yasui, Yasunori Itoh, et al. A polymorphism of matrix Gla protein gene is associated with kidney stones. J Urol, 2007,177:2361-2366.
16. Simone R, Andreas Fregin, Vytautas Ivaskevicius, et al. Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature, 2004,427:537-541.
17. Suhwarz UI, Ritchie MD, Bradford Y, et al. Genetic determinants of response to warfarin during initial anticoagulation. N Engl J Med, 2008, 358:999-1004.
18. Rost S, Pelz HJ, Menzel S, et al. Novel mutations in the VKORC1 gene of wild rats and mice-a response to 50 years of selection pressure by warfarin? BMC Genet, 2009, 10:4-10.
19. Loebstein R, Dvoskin I, Halkin H, et al. A coding VKORC1 Asp36Tyr polymor- phism predisposes to warfarin resistance. Blood, 2007, 109:2477-2480.
20. B. Nirmala Pudota, Eric L. Hommema, Kevin W. Hallgren, et al. Identification of sequences within the gamma-carboxylase that represent a novel contact site with vitamin K-dependent proteins and that are required for activity. J. Biol. Chem, 2001,276: 46878-46886.
21. Yibo Wang, Weili Zhang, Yuhui Zhang, et al. VKORC1 haplotypes are associated with arterial vascular diseases (stroke, coronary heart disease, and aortic dissection). Circulation, 2006, 113:1615-1617.
22. M. Teichert, LE. Visser, RHN van Schaik, et al. Vitamin K expoxide reductase complex subunit 1 (VKORC1) polymorphism and aortic calcification: the Rotterdam study. Arterio-sclerosis, Thrombosis, and Vascular Biology, 2008, 28:771-776.
23. Elizabeth A.Sconece, Tayyaba I. Khan, Hilary A. et al. The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen. Blood, 2005, 106: 2329-2331.
24．安瑞华，冯陶，郭应禄，等．维生素K缺乏对肾钙素一直草酸钙结石形成的影响．中华泌尿外科杂志，1995，16：583-585．
25．李浩勇，李凯，刘继红，等．苯丙酮香豆素对实验性大鼠肾草酸钙结石形成的影响．中华泌尿外科杂志，2003，24：663-665．
1. Stamatelou KK, Francis ME, Jones CA, et al. Time trends in reported prevalence of kidney stones in the United States: 1976-1994. Kidney Int, 2003, 63:1817-1823.
2. Indridason OS, Birgisson S, Edvardsson VO, et al. Epidemiology of kidney stones in Iceland: a population-based study. Scand J Urol Nephrol, 2006, 40: 215-220.
3． 叶章群．泌尿系结石研究现况与展望．中华实验外科杂志，2005，22：261-262．
4． 陈志强，孔德波．泌尿系结石的基因诊断和治疗．现代泌尿外科杂志，2008，13：1-4．
5. J.A. Sayer. The genetics of nephrolithiasis. Nephron Exp Nephrol, 2008, 110:37-43.
6. West B, Luke A, Durazo-Arvizu RA, et al. Metabolic syndrome and self-reported history of kidney stones: the National Health and Nutrition Examination Survey (NHANES Ⅲ) 1988-1994. Am J Kidney Dis, 2008, 51:741-747.
7．谷现恩，刘继红．尿石症．北京：中国医药科技出版社，2004，4-1．
8. Frick KK, Bushinsky DA. Molecular mechanisms of primary hypercalciuria. J Am Soc Nephrol, 2003, 14:1082-1095.
9. Bai SC, Favus MJ. Vitamin D and calcium receptors: links to hypercalciuria. Curr Opin Nephrol, 2003, 14:1082-1095.
10. Mensenkamp AR, Hoenderop JG, Bindels RJ. Recent advances in renal tubular calcium reabsorption. Cuee Opin Nephrol Hypertens, 2006, 15:524-529.
11. Vezzoli G, Rubinacci A, Bianchin C, et al. Intestinal calcium absorption is associated with bone mass in stone-forming women with idiopathic hypercalciuria. Am J Kidney Dis, 2003, 42:1177-1183.
12. Curhan GC, Willett WC, Rimm EB,et al. Family history and risk of kidney stones. J Am Soc Nephrol, 1997, 8: 1568-1573.
13. Loredo-Osti JC, Roslin NM, Tessier J, et al. Segregation of urine calcium excretion in families ascertained for nephrolithiasis: evidence for a major gene. Kidney Int, 2005, 68: 966-971.
14. Stechrnan MJ, Loh NY, Thakker RV. Genetics of hypercalciuric nephrolithiasis: renal stone disease. Ann NY Acad Sci, 2007, 1116:461-484.
15. Bushinsky DA, Frick KK, Neheke K. Genetic hypercalciuric stone forming rats. Curt Opin Nephrol Hypertens, 2006, 15:403-418.
16. Gambaro G, Vezzoli G, Casari G, et al. Genetics of hypercalciuria and calcium nepheolithiasis: from the rare monogenic to the common polygenic forms. Am J Kidney Dis, 2004, 44:963-986.
17. Moe OW, Bonny O. Genetic hypercalciuria. J Am Soc Nephrol, 2005, 16:729-745.
18. Reed BY, Gitomer WL, Heller HJ, et al. Identification and characterization of a gene with base substitutions associated with the absorptive hypercalciuria phenotype and low spinal bone density. J Clin Endocrinol Metab, 2002, 87:1476-1485.
19. Sands JM, Naruse M, Baum M, et al. Apical extracellular calcium/polyvalent cation-sensing receptor regulates vasopressin-elicited water permeability in rat kidney inner medullary collecting duct. J Clin Invest. 1997, 99:1399-1405.
20．杨奕，王少刚，叶章群，等．钙敏感受体基因第7外显子单核苷酸多态性与特发性高钙尿的关系．中华实验外科杂志，2006，23：588-590．
21. Vezzoli G, Tanini A. Influence of calcium-sensing receptor gene on urinary calcium excretion in stone-forming patients. J AM Soc Nephrol, 2002, 13:2517-2523.
22. Vezzoli G, Terranegra A, Arcidiacono T, et al. R990G polymorphism of calcium-sensing receptor does produce a gain-of-function and predispose to primary hyper-calciuria. Kidney Int. 2007, 71:1155-1162.
23．易广才，邵振堂，阮滨，等．维生素D受体基因内切酶位点多态性与孕妇骨密度和补钙的关系．中国优生与遗传杂志，2002，10：25-26．
24. Nishiji MA, Saori, Sugaya, et al. Association of vitamin Dreceptor gene polymorphism with urolithiasis. American Urology Association, Inc Volume 167(5) May 2002, 2188-2191.
25. Ouz Sylemezolu, M Musrlolu. Polymorphisms in the vitamin D receptor gene and the risk of calcium nephrolithiasis in children. Euro Urol, 2003, 44:150-154.
26. Gunes S, Bilen CY. Vitamin D receptor gene polymorphism in patients with urolithiasis. Urol Res, 2006, 34:47-52.
27. Heilberg IP, Teixeira SH, Martini, et al. Vitamin D receptor gene polymorphism and bone mineral density in hypercalciuric calcium stone-forming patients. Nephron, 2002, 90:51-57.
28. Hamant Kumar, Himanshu Chaudhary. Association of vitamin D and calcitonin receptor gene polymorphism in pediatric nephrolithiasis. Pedi. Neph. J IPNA, 2005, 10:467-472.
29．胡少群，刘继红，王少刚，等．维生素D受体基因多态性与草酸钙尿结石的关系．中华泌尿外科杂志，2004，25：155-157．
30. Favus MJ, Kamauskas AJ, Parks JH, et al. Peripheral blood monocyte vitamin D receptor levels are elevated in patients with idiopathic hypercalciuria. J Clin Endocrinol Metab. 2004, 89: 4937-4943.
31. Bushinsky DA, Frick K, Nehrke K. Genetic hypercalciuric stone forming rats. Curr Opin Nephrol Hypertens, 2006, 15:403-418.
32. Hoopes RR Jr, Middleton FA, Sen S, et al. Isolation and confirmation of a calcium excretion quantitative trait locus on chromosome 1 in genetic hypercalciuric stone-forming congenic rats. J Am Soc Nephrol, 2006, 17:1292-1304.
33. Hoenderop JG, van Leeuwen JP, van der Eerden BC, et al. Renal Ca~(2+) wasting, hyper-absorption, and reduced bone thickness in mice lacking TRPV5. J Clin Invest, 2003, 112: 1906-1914.
34. Suzuki Y, Pasch A, Bonny O, et al.Gain-of-function haplotype in the epithelial calcium channel TRPV6 is a risk factor for renal calcium stone formation. Hum Mol Genet, 2008, 17: 1613-1618.
35. Lalioti MD, Zhang J, Volkman HM, et al. Wnk4 controls blood pressure and potassium homeostasis via regulation of mass and activity of the distal convoluted tubule. Nat Genet, 2006, 38:1124-1132.
36. Silva IV, Cebotaru V, Wang H, et al. The CLC-5 knockout mouse model of Dent's disease has renal hypercalciuria and increased bone turn-over. J Bone Miner Res, 2003, 18:615-623.
37. Devuyst O, Pirson Y. Genetics of hypercalciuric stone forming diseases. Kidney Int, 2007, 72: 1065-1072.
38. Muller D, Hoenderop JG, Vennekens R, et al. Epithelial channel Ca~(2+) (ECAC1) in autosomal dominant idiopathic hypercalciuria. Nephrol Dial Transplant, 2002, 17:1614-1620.
39. Scheinman SJ, Cox JP, Llord SE, et al. Isolated hypercalciuria with mutation in CLCN-5: relevance to idiopathic hypercalciuria. Kidney Int, 2000, 57:232-239.
40. Milosevic D, Rinat C, Batinic D, et al. Genetic analysis-a diagnostic tool for primary hyperoxaluria type I. Pediatr Nephrol, 2002,17:896-898.
41. Pirulli D, Giordano M, Lessi M, et al. Detection of AGXT gene mutations by denaturing high-performance liquid chromatography for diagnosis of hyperoxaluria type I. Clin Exp Med, 2001,1:99-104.
42. Rumsby G, Williams E, Coulter-Maekie M. Evaluation of mutation screening as a first line test for the diagnosis of the primary hyperroxalurias.Kidney Int, 2004, 66:959-963.
43. Cramer SD, Ferree PM, Lin K, et al. The gene encoding hydroxypyruvate reductase (GRHPR) is mutated in patients with primary hyperoxaluria type Ⅱ. Hum Mol Genet,1999,8:2063-2069.
44. Cregeen DP, Willams EL, Hulton S, et al. Molecular analysis of the glyoxylate reductase (GRHPR) gene and description of mutations underlying primary hyperoxaluria type Ⅱ. Hum Mutat, 2003, 22:497-451.
45. Webster KE, Ferree PM, Holmes RP, et al. Identification of missense, nonsense, and deletion mutations in the GRHPR gene in patients with primary hyperoxaluria type Ⅱ.Hum Genet, 2000, 107:176-185.
46. Aronson PS. Essential roles of CFEX-mediated Cl (-)-oxalate exchange in proximal tubule NaCl transport and prevention of urolithiasis. Kidney Int, 2006, 70: 1207-1213.
47. Cochat P, Liutkus A, Fargue S, et al. Primary hyperoxaluria type 1: still challenging!Pediatr Nephrol, 2006, 21: 1075-1081.
48. Troxel SA, Sidhu H, Kaul P, et al. Intestinal Oxalobacter formigenes colonization in calcium oxalate stone formers and its relation to urinary oxalate. J Endourol, 2003,17:173-176.
49. Carr G, Sayer JA, Simmons NL. Expression and localisation of the pyrophosphate transporter, ANK, in murine kidney cells. Cell Physiol Biochem, 2007, 20: 507-516.
50. Skopkova Z, Hrabincova E, Stastna S, et al. Molecular genetic analysis of SLC3A1 and SLC7A9 genes in Crech and Slovak cystinuric patients. Ann Hum Genet, 2005,69:501-507.
51. Brauers E, Vester U, Zerres K, et al. Search for mutations in SLC1A5 (19q13) incystinuria patients. J Inherit Metab Dis, 2005, 28:1169-1171.
52. Botzenhart E, Vester U, Schmidt C, et al. Cystinuria in children: distribution and frequencies of mutations in the SLC3A1 and SLC7A9 gene. Kidney Int, 2002,62:1136-1142.
53. Fry AC, Karet FE. Inherited renal acidoses.Physiology, 2007, 22:202-211.
54. Carr G, Sayer JA, Simmons NL. Expression and localisation of the pyrophosphate transporter, ANK, in murine kidney cells. Cell Physiol Biochem, 2007, 20:507-516.
55. Jaggi M, Nakagawa Y, Zipperle L, et al. Tamm-Horsfall protein in recurrent calcium kidney stone formers with positive family history: abnormalities in urinary excretion,molecular structure and function. Urol Res, 2007, 35: 55-62.
56. Wolf MT, Zalewski I, Martin FC, et al. Mapping a new suggestive gene locus for autosomal dominant nephrolithiasis to chromosome 9q33.2-q34.2 by total genome search for linkage. Nephrol Dial Transplant, 2005, 20: 909-914.
57. Gao B, Yasui T, Itoh Y, et al. A polymorphism of matrix Gla protein gene is associated with kidney stones. J Urol, 2007, 177: 2361-2365.
58. Eliane H. T, Aleksandra Radenovic, David Sivak, et al. Controlling DNA capture and propagation through artificial nanopores. Nano Lett. 2007, 8:1-6.
2. MJ Stechman, NY Loh, RV Thakker. Genetics of hypercalciuric nephrolithiasis: renal stone disease. Annals of the New York Academy of Sciences, 2007, 1116:461-467.
3．朱绍兴，章咏裳，刘继红．晶体表面结合蛋白对草酸钙晶体生长的抑制作用．中华泌尿外科杂志，1998，19(8)：457-459．
4. Liu J, Wang T, Chen J, et al. Decreased inhibitory activity of prothrombin to calcium oxalate crystallization by specific chemical modification of its γ-carboxyglutamic acid residues. Urology, 2006, 67:201-203.
5. Grover PK, Miyazawa K, Coleman M, et al. Renal prothrombin mRNAis significantly decreased in a hyperoxaluric rat model of nephrolithiasis. J Pathol, 2006, 210:273-276.
6. Liu J, Chen J, Wang T, et al. Effects of urinary prothrombin fragment lin the formation of calcium oxalate calculus. J Urol, 2005, 173:113-116.
7. Bing Gao, Takahiro Yasui, Yasunori Itoh, et al. A polymorphism of matrix Gla protein gene is associated with kidney stones. J Urol, 2007, 177:2361-2365.
8. Kathleen L. Berkner. The vitamin K-dependent caroxylase. Annual Review of Nutrition, 2005, 25:127-149.
9. Tao Li, Chun-Yun Chang, Da-Yun Jin, et al. Identification of the gene for vitamin K epoxide reductase. Nature, 2004, 427:541-544.
10. Jian-Ke, Tie, Christopher Nicchitta, Gunnar von Heijne, et al. Membrane Topology Mapping of Vitamin K Epoxide Reductase by in Vitro Translation/Co translocation. J. Biol. Chem, 2005, 280:16410-16415.
11. Anderea A, Garcia, Pieter H. Reitsma. VKORC1 and the Vitamin K Cycle. In: Gerald, eds. Vitamin K and hormons Volum 78. London: Academic, 2008.23
12. Simone R, Andreas Fregin, Vytautas Ivaskevicius, et al. Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature, 2004, 427:537-541.
13. Chen JH, Liu JH, Zhang YS, et al. Decreased renal vitamin K-dependent gamma-glutamyl carboxylase activity in calcium oxalate calculi patients. Chin Med J (Engl),2003, 116:569-571.
1. Saeed R Khan, Dirk J. Modulators of urinary stone formation. Fornt Biosci, 2004, 9:1450-1482.
2. Liu J, Chen J, Wang T, et al. Effects of urinary prothrombin fragment lin the formation of calcium oxalate calculus. J Urol, 2005, 173:113-116.
3. Chen JH, Liu JH, Zhang YS, et al. Decreased renal vitamin K-dependent gamma-glutamyl carboxylase activity in calcium oxalate calculi patients. Chin Med J (Engl), 2003, 116:569-571.
4. Gary M. Wood, J. W. Suttie. Vitamin K-dependent Carboxylase. J Biol Chem. 1988, 263:3234-3239.
5. Liu J, Wang T, Chen J, et al. Decreased inhibitory activity of prothrombin to calcium oxalate crystallization by specific chemical modification of its γ-carboxyglutamic acid residues. Urology, 2006, 67:201-203.
6. Stapleton AMF, Timme TL, Ryall RL. The gene expression ofprothombin in the human kidney: its potential relevance to kidney stone disease. Bri J Urol, 1998; 61:666-668.
7. Bing Gao, Takahiro Yasui, Yasunori Itoh, et al. A polymorphism of matrix Gla protein gene is associated with kidney stones. J Urol, 2007, 177:2361-2365.
8．王少刚，刘继红，章咏裳．草酸钙结石患者尿中蛋白结合型γ-羧基谷氨酸的检测意义．中华泌尿外科杂志，2002，23：428-430．
9. Furie B, Bouchard BA, Furie BC. Vitamin K-dependent biosynthesis of γ-carboxy-glutamic acid. Blood, 1999, 93:1798-1808.
10. Kumar V, Farell G, Lieske JC. Whole urinary proteins coat calcium oxalate monohydrate crystals to greatly decrease their adhesion to renal cells. J Urol. 2003, 170:221-225.
11. Friedman PA, Mitch WE, Silva P. Localization of renal vitamin K-dependent gamma-glutamyl carboxylase to tubule cells. J Biol Chem 1982, 257:11037-11044.
12. Berkner KL, McNally BA. Purification of vitamin K-dependent carboxylase from cultured cells. Methods Enzymol, 1997;282:313-333
13. Angayarkanni N, Selvam R, Enhanced renal vitamin-K-dependent gamma- glutarnyl carboxylase activity in experimental rat urolithiasis. Eur Urol, 1998, 33:116-120.
14．杨俊，刘继红，郭小林，等．草酸钙尿石症患者肾组织VKDC基因表达及其意义．临床泌尿外科杂志，2007，22：736-738．
15. Wadelius M, Chen LY, Downes K, et al. Common VKORC1 and GGCX polymorphisms associated with warfarin dose. Pharmacogenomics J, 2005, 5:262-270.
16．龚小新，刘继红，郭小林，等．草酸钙尿石患者VKDC结构域基因突变的研究．中华实验外科杂志，2007，24：1606-1607．
17. Chen DH, Kaung HL, Miller CM, et al: Microarray analysis of changes in renal phenotype in the ethylene glycol rat model of urolithiasis: potential and pitfalls. BJU Int, 2004, 94:637-650.
18. Grover PK, Miyazawa K, Coleman M, et al: Renal prothrombin mRNA is significantly decreased in a hyperoxaluric rat model of nephrolithiasis. J Pathol, 2006, 210:273-281.
1. Stafford DW. The vitamin K cycle [J]. J Thromb Haemost. 2005; 3(8):1873-1878.
2. Romero EE, Marvi U, Niman ZE, et al. The vitamin K-dependent gamma-glutamyl carboxylase gene contains a TATA-less promoter with a novel upstream regulatory element [J].Blood. 2003; 102(4):1333-1339.
3. Romero EE, Velazquez-Estades LJ, Deo R, et al. Cloning of rat vitamin K-dependent gamma-glutamyl carboxylase and developmentally regulated gene expression in postimplantation embryos [J]. Exp Cell Res. 1998; 243(2):334-346.
4．杨俊，刘继红，郭小林，等．草酸钙尿石症患者肾组织VKDC基因表达的研究[J]．临床泌尿外科杂志．2007；22(10)：736-738．
5．王少刚，刘继红，章咏裳．草酸钙结石患者尿中蛋白结合型γ-羧基谷氨酸的检测意义[J]．中华泌尿外科杂志．2002；23(7)：428-430．
6．陈俊汇，刘继红，章咏裳，等．草酸钙尿结石患者肾组织维生素K依赖羧化酶活性的研究[J]．中华泌尿外科杂志．2002；23(12)：725-727．
7. Chen Z, Kai G, Liu X, et al. cDNA cloning and characterization of a mannose-binding lectin from Zingiber officinale Roscoe rhizomes. J Biosci. 2005, 30:213-220.
8. Chung Moh M, Hoon Lee L, Shen S. Cloning and characterization of hepaCAM a novel Ig-like cell adhesion molecule suppressed in human hepatocellular carcinoma. J Hepatol. 2005,42:833-841.
9．张陆，惠汝太．3’非翻译区在转录后调控中的作用．中国分子心脏病学杂志，2005，5：619-624．
10. Lorenzo Malquori, Laura Carsetti, Giovina Ruberti. The 3'-UTR of the human CTLA4 mRNA stability and translational efficiency. Bioch. Biop. Acta. 2007,10:1111-1116.
11. Flavio Mignone, Carmela Gissi, Sabino Liuni, et al. Umtranslated regions of mRNAs. Genome Biology. 2002, 3:0004.1-0004.10.
12. Shi Tongdong, Wu Yuzhang, Zhu Xihua. 3'-Untranslated region of eukaryotic mRNA in gene regulation. Prog Biochem Biophys, 1998, 25:195-197.
13. Romero EE, Velazquez-Estades LJ, Deo R, et al. Cloning of rat vitamin K-dependent gamma-glutamy] carboxylase and developmentally regulated gene expression in postimplantation embryos [J]. Exp Cell Res. 1998, 243(2):334-346.
14. Prezioso D, Di Martino M, Galasso R, et al. Laboratory assessment [J]. Urol Int. 2007,79 Suppl 1:20-25.
1. Saeed R Khan, Dirk J. Modulators of urinary stone formation, 2004, 9:1450-1452.
2． 叶章群．泌尿系结石研究现况与展望．中华实验外科杂志，2005，22：261-262．
3. Kathleen L. Berkner. The vitamin K-dependent caroxylase. Annual Review of Nutrition, 2005, 25:127-149.
4. Anderea A, Garcia, Pieter H. Reitsma. VKORC1 and the Vitamin K Cycle. In: Gerald, eds. Vitamin K and hormons Volum 78. London: Academic, 2008.23
5. Tao Li, Chun-Yun Chang, Da-Yun Jin, et al. Identification of the gene for vitamin K epoxide reductase. Nature, 2004, 427:541-546.
6. Jian-Ke, Tie, Christopher Nicchitta, Gunnar von Heijne, et al. Membrane Topology Mapping of Vitamin K Epoxide Reductase by in Vitro Translation/Co translocation. J. Biol. Chem, 2005, 280:16410-16415.
7. Oldenburg J, Marinova M, Muller C., et al. The Vitamin K circle. Vitam Horm, 2008, 78: 35-62.
8. D. Darghouth, KW. Hallgren, RL. Shtofrnan, et al. Compound heterozygosity of novel missense mutations in the gamma-glutamylcarboxylase gene causes hereditary combined vitamin K-dependent coagulation factor deficiency. Blood, 2006, 108:1925-1931.
9. Nadeem Wajih, David C. Sane, Susan M. Huston, et al. Engineering of a recombinant vitamin K-dependent gamma-carboxylation system with enhanced gamma-carboxy-glutamic acid forming capacity. J. Biol. Chem, 2005, 280:10540-10547.
10. MJ Stechman, NY Loh, RV Thakker. Genetics of hypercalciuric nephrolithiasis: renal stone disease. Annals of the New York Academy of Sciences, 2007, 1116:461
11．朱绍兴，章咏裳，刘继红．晶体表面结合蛋白对草酸钙晶体生长的抑制作用．中华泌尿外科杂志，1998，19(8)：457-459．
12. Liu J, Wang T, Chen J, et al. Decreased inhibitory activity of prothrombin to calcium oxalate crystallization by specific chemical modification of its y-carboxyglutamic acid residues. Urology, 2006, 67:201-203.
13. Grover PK, Miyazawa K, Coleman M, et al. Renal prothrombin mRNAis significantly decreased in a hyperoxaluric rat model of nephrolithiasis. J Pathol, 2006, 210:273-276.
14. Liu JH, Chen JH, Wang T, et al. Effects of urinary prothrombin fragment 1 in the formation of calcium oxalate calculus. J Urol, 2005,173:113-116
15. Bing Gao, Takahiro Yasui, Yasunori Itoh, et al. A polymorphism of matrix Gla protein gene is associated with kidney stones. J Urol, 2007,177:2361-2366.
16. Simone R, Andreas Fregin, Vytautas Ivaskevicius, et al. Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature, 2004,427:537-541.
17. Suhwarz UI, Ritchie MD, Bradford Y, et al. Genetic determinants of response to warfarin during initial anticoagulation. N Engl J Med, 2008, 358:999-1004.
18. Rost S, Pelz HJ, Menzel S, et al. Novel mutations in the VKORC1 gene of wild rats and mice-a response to 50 years of selection pressure by warfarin? BMC Genet, 2009, 10:4-10.
19. Loebstein R, Dvoskin I, Halkin H, et al. A coding VKORC1 Asp36Tyr polymor- phism predisposes to warfarin resistance. Blood, 2007, 109:2477-2480.
20. B. Nirmala Pudota, Eric L. Hommema, Kevin W. Hallgren, et al. Identification of sequences within the gamma-carboxylase that represent a novel contact site with vitamin K-dependent proteins and that are required for activity. J. Biol. Chem, 2001,276: 46878-46886.
21. Yibo Wang, Weili Zhang, Yuhui Zhang, et al. VKORC1 haplotypes are associated with arterial vascular diseases (stroke, coronary heart disease, and aortic dissection). Circulation, 2006, 113:1615-1617.
22. M. Teichert, LE. Visser, RHN van Schaik, et al. Vitamin K expoxide reductase complex subunit 1 (VKORC1) polymorphism and aortic calcification: the Rotterdam study. Arterio-sclerosis, Thrombosis, and Vascular Biology, 2008, 28:771-776.
23. Elizabeth A.Sconece, Tayyaba I. Khan, Hilary A. et al. The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen. Blood, 2005, 106: 2329-2331.
24．安瑞华，冯陶，郭应禄，等．维生素K缺乏对肾钙素一直草酸钙结石形成的影响．中华泌尿外科杂志，1995，16：583-585．
25．李浩勇，李凯，刘继红，等．苯丙酮香豆素对实验性大鼠肾草酸钙结石形成的影响．中华泌尿外科杂志，2003，24：663-665．
1. Stamatelou KK, Francis ME, Jones CA, et al. Time trends in reported prevalence of kidney stones in the United States: 1976-1994. Kidney Int, 2003, 63:1817-1823.
2. Indridason OS, Birgisson S, Edvardsson VO, et al. Epidemiology of kidney stones in Iceland: a population-based study. Scand J Urol Nephrol, 2006, 40: 215-220.
3． 叶章群．泌尿系结石研究现况与展望．中华实验外科杂志，2005，22：261-262．
4． 陈志强，孔德波．泌尿系结石的基因诊断和治疗．现代泌尿外科杂志，2008，13：1-4．
5. J.A. Sayer. The genetics of nephrolithiasis. Nephron Exp Nephrol, 2008, 110:37-43.
6. West B, Luke A, Durazo-Arvizu RA, et al. Metabolic syndrome and self-reported history of kidney stones: the National Health and Nutrition Examination Survey (NHANES Ⅲ) 1988-1994. Am J Kidney Dis, 2008, 51:741-747.
7．谷现恩，刘继红．尿石症．北京：中国医药科技出版社，2004，4-1．
8. Frick KK, Bushinsky DA. Molecular mechanisms of primary hypercalciuria. J Am Soc Nephrol, 2003, 14:1082-1095.
9. Bai SC, Favus MJ. Vitamin D and calcium receptors: links to hypercalciuria. Curr Opin Nephrol, 2003, 14:1082-1095.
10. Mensenkamp AR, Hoenderop JG, Bindels RJ. Recent advances in renal tubular calcium reabsorption. Cuee Opin Nephrol Hypertens, 2006, 15:524-529.
11. Vezzoli G, Rubinacci A, Bianchin C, et al. Intestinal calcium absorption is associated with bone mass in stone-forming women with idiopathic hypercalciuria. Am J Kidney Dis, 2003, 42:1177-1183.
12. Curhan GC, Willett WC, Rimm EB,et al. Family history and risk of kidney stones. J Am Soc Nephrol, 1997, 8: 1568-1573.
13. Loredo-Osti JC, Roslin NM, Tessier J, et al. Segregation of urine calcium excretion in families ascertained for nephrolithiasis: evidence for a major gene. Kidney Int, 2005, 68: 966-971.
14. Stechrnan MJ, Loh NY, Thakker RV. Genetics of hypercalciuric nephrolithiasis: renal stone disease. Ann NY Acad Sci, 2007, 1116:461-484.
15. Bushinsky DA, Frick KK, Neheke K. Genetic hypercalciuric stone forming rats. Curt Opin Nephrol Hypertens, 2006, 15:403-418.
16. Gambaro G, Vezzoli G, Casari G, et al. Genetics of hypercalciuria and calcium nepheolithiasis: from the rare monogenic to the common polygenic forms. Am J Kidney Dis, 2004, 44:963-986.
17. Moe OW, Bonny O. Genetic hypercalciuria. J Am Soc Nephrol, 2005, 16:729-745.
18. Reed BY, Gitomer WL, Heller HJ, et al. Identification and characterization of a gene with base substitutions associated with the absorptive hypercalciuria phenotype and low spinal bone density. J Clin Endocrinol Metab, 2002, 87:1476-1485.
19. Sands JM, Naruse M, Baum M, et al. Apical extracellular calcium/polyvalent cation-sensing receptor regulates vasopressin-elicited water permeability in rat kidney inner medullary collecting duct. J Clin Invest. 1997, 99:1399-1405.
20．杨奕，王少刚，叶章群，等．钙敏感受体基因第7外显子单核苷酸多态性与特发性高钙尿的关系．中华实验外科杂志，2006，23：588-590．
21. Vezzoli G, Tanini A. Influence of calcium-sensing receptor gene on urinary calcium excretion in stone-forming patients. J AM Soc Nephrol, 2002, 13:2517-2523.
22. Vezzoli G, Terranegra A, Arcidiacono T, et al. R990G polymorphism of calcium-sensing receptor does produce a gain-of-function and predispose to primary hyper-calciuria. Kidney Int. 2007, 71:1155-1162.
23．易广才，邵振堂，阮滨，等．维生素D受体基因内切酶位点多态性与孕妇骨密度和补钙的关系．中国优生与遗传杂志，2002，10：25-26．
24. Nishiji MA, Saori, Sugaya, et al. Association of vitamin Dreceptor gene polymorphism with urolithiasis. American Urology Association, Inc Volume 167(5) May 2002, 2188-2191.
25. Ouz Sylemezolu, M Musrlolu. Polymorphisms in the vitamin D receptor gene and the risk of calcium nephrolithiasis in children. Euro Urol, 2003, 44:150-154.
26. Gunes S, Bilen CY. Vitamin D receptor gene polymorphism in patients with urolithiasis. Urol Res, 2006, 34:47-52.
27. Heilberg IP, Teixeira SH, Martini, et al. Vitamin D receptor gene polymorphism and bone mineral density in hypercalciuric calcium stone-forming patients. Nephron, 2002, 90:51-57.
28. Hamant Kumar, Himanshu Chaudhary. Association of vitamin D and calcitonin receptor gene polymorphism in pediatric nephrolithiasis. Pedi. Neph. J IPNA, 2005, 10:467-472.
29．胡少群，刘继红，王少刚，等．维生素D受体基因多态性与草酸钙尿结石的关系．中华泌尿外科杂志，2004，25：155-157．
30. Favus MJ, Kamauskas AJ, Parks JH, et al. Peripheral blood monocyte vitamin D receptor levels are elevated in patients with idiopathic hypercalciuria. J Clin Endocrinol Metab. 2004, 89: 4937-4943.
31. Bushinsky DA, Frick K, Nehrke K. Genetic hypercalciuric stone forming rats. Curr Opin Nephrol Hypertens, 2006, 15:403-418.
32. Hoopes RR Jr, Middleton FA, Sen S, et al. Isolation and confirmation of a calcium excretion quantitative trait locus on chromosome 1 in genetic hypercalciuric stone-forming congenic rats. J Am Soc Nephrol, 2006, 17:1292-1304.
33. Hoenderop JG, van Leeuwen JP, van der Eerden BC, et al. Renal Ca~(2+) wasting, hyper-absorption, and reduced bone thickness in mice lacking TRPV5. J Clin Invest, 2003, 112: 1906-1914.
34. Suzuki Y, Pasch A, Bonny O, et al.Gain-of-function haplotype in the epithelial calcium channel TRPV6 is a risk factor for renal calcium stone formation. Hum Mol Genet, 2008, 17: 1613-1618.
35. Lalioti MD, Zhang J, Volkman HM, et al. Wnk4 controls blood pressure and potassium homeostasis via regulation of mass and activity of the distal convoluted tubule. Nat Genet, 2006, 38:1124-1132.
36. Silva IV, Cebotaru V, Wang H, et al. The CLC-5 knockout mouse model of Dent's disease has renal hypercalciuria and increased bone turn-over. J Bone Miner Res, 2003, 18:615-623.
37. Devuyst O, Pirson Y. Genetics of hypercalciuric stone forming diseases. Kidney Int, 2007, 72: 1065-1072.
38. Muller D, Hoenderop JG, Vennekens R, et al. Epithelial channel Ca~(2+) (ECAC1) in autosomal dominant idiopathic hypercalciuria. Nephrol Dial Transplant, 2002, 17:1614-1620.
39. Scheinman SJ, Cox JP, Llord SE, et al. Isolated hypercalciuria with mutation in CLCN-5: relevance to idiopathic hypercalciuria. Kidney Int, 2000, 57:232-239.
40. Milosevic D, Rinat C, Batinic D, et al. Genetic analysis-a diagnostic tool for primary hyperoxaluria type I. Pediatr Nephrol, 2002,17:896-898.
41. Pirulli D, Giordano M, Lessi M, et al. Detection of AGXT gene mutations by denaturing high-performance liquid chromatography for diagnosis of hyperoxaluria type I. Clin Exp Med, 2001,1:99-104.
42. Rumsby G, Williams E, Coulter-Maekie M. Evaluation of mutation screening as a first line test for the diagnosis of the primary hyperroxalurias.Kidney Int, 2004, 66:959-963.
43. Cramer SD, Ferree PM, Lin K, et al. The gene encoding hydroxypyruvate reductase (GRHPR) is mutated in patients with primary hyperoxaluria type Ⅱ. Hum Mol Genet,1999,8:2063-2069.
44. Cregeen DP, Willams EL, Hulton S, et al. Molecular analysis of the glyoxylate reductase (GRHPR) gene and description of mutations underlying primary hyperoxaluria type Ⅱ. Hum Mutat, 2003, 22:497-451.
45. Webster KE, Ferree PM, Holmes RP, et al. Identification of missense, nonsense, and deletion mutations in the GRHPR gene in patients with primary hyperoxaluria type Ⅱ.Hum Genet, 2000, 107:176-185.
46. Aronson PS. Essential roles of CFEX-mediated Cl (-)-oxalate exchange in proximal tubule NaCl transport and prevention of urolithiasis. Kidney Int, 2006, 70: 1207-1213.
47. Cochat P, Liutkus A, Fargue S, et al. Primary hyperoxaluria type 1: still challenging!Pediatr Nephrol, 2006, 21: 1075-1081.
48. Troxel SA, Sidhu H, Kaul P, et al. Intestinal Oxalobacter formigenes colonization in calcium oxalate stone formers and its relation to urinary oxalate. J Endourol, 2003,17:173-176.
49. Carr G, Sayer JA, Simmons NL. Expression and localisation of the pyrophosphate transporter, ANK, in murine kidney cells. Cell Physiol Biochem, 2007, 20: 507-516.
50. Skopkova Z, Hrabincova E, Stastna S, et al. Molecular genetic analysis of SLC3A1 and SLC7A9 genes in Crech and Slovak cystinuric patients. Ann Hum Genet, 2005,69:501-507.
51. Brauers E, Vester U, Zerres K, et al. Search for mutations in SLC1A5 (19q13) incystinuria patients. J Inherit Metab Dis, 2005, 28:1169-1171.
52. Botzenhart E, Vester U, Schmidt C, et al. Cystinuria in children: distribution and frequencies of mutations in the SLC3A1 and SLC7A9 gene. Kidney Int, 2002,62:1136-1142.
53. Fry AC, Karet FE. Inherited renal acidoses.Physiology, 2007, 22:202-211.
54. Carr G, Sayer JA, Simmons NL. Expression and localisation of the pyrophosphate transporter, ANK, in murine kidney cells. Cell Physiol Biochem, 2007, 20:507-516.
55. Jaggi M, Nakagawa Y, Zipperle L, et al. Tamm-Horsfall protein in recurrent calcium kidney stone formers with positive family history: abnormalities in urinary excretion,molecular structure and function. Urol Res, 2007, 35: 55-62.
56. Wolf MT, Zalewski I, Martin FC, et al. Mapping a new suggestive gene locus for autosomal dominant nephrolithiasis to chromosome 9q33.2-q34.2 by total genome search for linkage. Nephrol Dial Transplant, 2005, 20: 909-914.
57. Gao B, Yasui T, Itoh Y, et al. A polymorphism of matrix Gla protein gene is associated with kidney stones. J Urol, 2007, 177: 2361-2365.
58. Eliane H. T, Aleksandra Radenovic, David Sivak, et al. Controlling DNA capture and propagation through artificial nanopores. Nano Lett. 2007, 8:1-6.