Klotho基因G-395A和C1818T多态性与胃癌遗传易感性的研究

The associations between the Klotho gene G-395A and C1818T polymorphisms and the risk of gastric cancer

目的:探讨Klotho基因单核苷酸多态性(SNPs)与江苏人群胃癌遗传易感性的关系。方法:采用病例-对照的分子流行病学方法,以聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法对151例胃癌和145例健康人群的Klotho基因启动子区域G-395A和外显子4区C1818T进行基因分型,并比较不同基因型与胃癌发病危险的关系。结果:G-395A多态性位点中GA+AA基因型在胃癌中的频率(39.7%)显著高于对照组(28.2%),携带GA+AA变异基因型者患胃癌的危险性是GG的1.66倍(调整的比值比:95℅可信区间:1.02～2.72)。分层分析显示,此危险在50岁以下的男性人群中更为显著,同时在吸烟和饮酒人群中也有显著的关系。C1818T多态性在胃癌和对照人群的分布无显著差别。两个多态性位点处于连锁不平衡(D=0.449,r2=0.187),在对照人群中均符合Hardy-Weniberg平衡,4种单倍体在病例和对照组中的分布均无显著性差异。结论:在中国江苏汉族人群中,Klotho基因启动子区多态位点G-395A变异显著增加江苏人群患胃癌的危险性,外显子4区C1818T多态性则无明显影响。

Objective：To investigate the association between Klotho gene polymorphisms and the risk of gastric cancer in Jiangsu population. Methods：In a case-control study of 151 patients and 145 controls,we genotyped G-395A in the promoter region and C1818T in exon 4 of Klotho gene by PCR-restriction fragment length polymorphism （PCR-RFLP） methods. The association between the genetic polymorphisms and the risk of the cancer was further examined by multivariate analysis. Results：The frequency of the A allele of G-395A polymorphism in patients（39.7%） was significantly higher than that in controls（28.2%,P = 0.038）, with the adjusted OR= 1.66 and 95 % CI 1.02-2.72, which was more pronounced among subgroups of youger males, smokers and drinkers. How- ever,the frequency of C1818T did not show any significant difference between the patients and control subjects （P = O.gO）. The two polymorphisms were in linkage disequilibrium（D -- 0.449,r = 0.187） and in compliance with Hardy-Weniberg equilibrium in control. None of the haplotypes were significantly associated with the presence of the gastric cancer. Conclusion：The G-395A polymorphism in Klotho gene may positively contribute to the etiology of gastric cancer in Jiangsu population.