XPC基因多态性与男性不育的相关性研究

Ala499Val(C>T) and Lys939Gln(A>C) polymorphisms of the XPC gene:Their correlation with male infertility

目的:位于XPC基因外显子区域Ala499Val(C>T)和Lys939Gln(A>C)两个非同义突变的单核苷酸多态性位点在人群中研究广泛,具有潜在的功能性,其多态的变化影响到XPC基因的结构和功能,进而影响到DNA损伤修复率。本文探讨了这两个位点基因多态性在中国汉族人群中的分布及其与男性不育发病风险的关联。方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法,分析318例男性不育患者和228例正常对照男性中XPC基因两个多态性位点的基因分型和等位基因频率,以及这两个位点单独和联合作用与男性不育的相关性。结果:在Ala499Val(C>T)多态性位点中,CC、CT、TT三种基因型频率在病例和对照组中的分布存在显著性差异(P=0.020)。携带TT基因型的个体罹患男性不育的风险是CC基因型个体的0.49倍(95%CI=0.23～0.88),是(CC+CT)基因型个体的0.39倍(95%CI=0.22～0.71)。Lys939Gln(A>C)多态性位点与男性不育的患病风险无显著性关联。联合两个位点分析,个体携带1～4个危险位点患男性不育的风险是携带零个的2.75倍(95%CI=1.50～5.04)。结论:XPC基因Ala499Val(C>T)基因多态性与男性不育的发病风险存在关联,可能是我国汉族人群男性不育的遗传易感因素之一。

Objective：The Ala499Val（CT）and Lys939Gln（AC）of the XPC gene are two potentially functional nonsy-nonymous polymorphisms,which affect the rate of DNA repair and might change XPC production and activity.This study aimed to explore the distribution of these two polymorphisms in the Chinese Han population and their relationship with male infertility.Methods：We genotyped the two polymorphisms of the XPC gene by the PCR-restriction fragment length polymorphism（PCR-RFLP）method in 318 infertile patients and 228 fertile male controls,detected the frequency of the alleles,and analyzed both the individual and the joint contribution of the two polymorphisms to male infertility.Results：For the Ala499Val（CT）polymorphism,the frequencies of the CC,CT,and TT genotypes were significantly different in distribution between the patients and the controls（P = 0.020）.Males with the TT genotype had a lower risk of male infertility than those with the CC genotype（adjusted OR = 0.49,95% CI：0.23-0.88）,and even lower than those with both CC and CT genotypes（adjusted OR = 0.39,95% CI：0.22-0.71）.The Lys939Gln（AC）polymorphism was not related with male infertility.The combined genotype analysis showed that the individuals with 1-4 risk alleles had a significantly higher risk of male infertility（adjusted OR = 2.75,95% CI = 1.50-5.04）than those with 0 risk allele.Conclusion：The Ala499Val（CT）polymorphism of the XPC gene is correlated with male infertility and may be a potential genetic risk factor for male infertility in the Chinese Han population.