硫酸乙酰肝素蛋白多糖基因多态性与草酸钙结石易感性的关系

Heparan sulfate proteoglycan gene polymorphism and genetic susceptibility to calcium oxalate nephrolithiasis

目的探讨硫酸乙酰肝素蛋白多糖(HSPG)基因多态性与中国汉族人群草酸钙肾结石易感性的关系。方法以病例对照研究方法,提取143例草酸钙肾结石患者及157例健康对照者外周血标本基因组DNA,应用聚合酶链反应-限制性片断长度多态性(PCR-RFLP)分析技术,检测并分析HPSG基因rs3767140位点单核甘酸多态性与草酸钙肾结石的关系。结果HPSG基因等位基因频率分布符合Hardy-Weinberg平衡定律,结石组GG+GT、TT基因型分布频率分别为69.23%、30.77%,健康对照组分别为79.62%、20.38%(P<0.05),TT基因型个体患结石的风险是其它基因型的1.736倍(95%CI=1.026～2.938),结石组与对照组等位基因G、T分布频率分别为:45.10%、55.90%和54.14%、45.86%(P<0.05),未发现HPSG基因多态性与草酸钙结石的复发相关。结论HPSG基因多态性与草酸钙尿路结石有相关关系,TT基因型可作为草酸钙结石危险因素的标志。

Objective To explore the potential association between the heparan sulfate proteoglycan gene （HSPG） polymorphism and genetic susceptibility to calcium oxalate nephrolithiasis in the Chinese Han population. Methods 143 patients diagnosed with calcium oxalate urolithiasis were enrolled in this study. In addition,157 age-matched healthy controls were enrolled. Genomic DNA was extracted from blood samples. Based on a case-control study,HSPG polymorphism （rs3767140） was determined by polymerase chain reaction and restriction fraction length polymorphism（PCR-RFLP） with BamHⅠ digestion. Results Distribution frequencies of site rs3767140 genotype and alleles in the two groups followed the Hardy-Weinberg equilibrium. Distribution frequencies of the GG＋GT and TT genotypes were 69.23% and 30.77% in the oxalate calcium urolithiasis group and 79.62% and 20.38% in the healthy control group. Differences between the two groups were statistically significant（P〈0.05）. Distribution frequencies of the G and T alleles in the two groups were respectively 45.10% and 55.90% and 54.14% and 45.86% with statistical differences （P〈0.05）. Subjects with the TT genotype yielded a 1.736-fold increased risk for calcium oxalate nephrolithiasis,compared with subjects with the GT＋GG genotype（OR=1.736,95% CI=1.026～2.938）,however,we did not find an association between HSPG gene polymorphism and the possibility of stone recurrence. Conclusion There is a significant association between HSPG gene polymorphism and calcium oxalate nephrolithisis,and the TT genotype may be a good genetic marker.