OGG1 Ser326Cys polymorphism interacts with cigarette smoking to increase oxidative DNA damage in human sperm and the risk of male infertility
OGG1 Ser326Cys polymorphism interacts with cigarette smoking to increase oxidative DNA damage in human sperm and the risk of male infertility
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OGG1 Ser326Cys 多态性与吸烟相互作用，增加人类精子的氧化 DNA 损伤和男性不育的风险。
DOI：
10.1016/j.toxlet.2013.01.017
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发表时间：
2013-04-12
影响因子：
3.5
通讯作者：
Gu, Aihua
中科院分区：
文献类型：
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作者：
Ji, Guixiang;Yan, Lifeng;Gu, Aihua
8-氧鸟嘌呤DNA糖基化酶1（OGG 1）在修复烟草等化学物质引起的DNA氧化损伤中起重要作用。本研究检测了OGG 1 Ser 326 Cys多态性和吸烟（单独或联合）对精子DNA氧化损伤和男性不育风险的影响。本研究共招募了620名特发性不育受试者和480名生育对照者。采用流式细胞仪免疫荧光法检测精子8-羟基脱氧鸟嘌呤（8-OHdG），采用基于芯片的Taq-Man基因分型技术，通过OpenArray平台进行基因分型。吸烟和OGG 1基因多态性均能影响精子8-OHdG水平。变异Cys/Cys纯合子携带者精子8-OHdG水平高于野生型纯合子携带者（Ser/Ser）。分层分析发现，OGG 1多态性与精子8-OHdG水平之间的关联仅在吸烟包年数>= 5的吸烟者中观察到，而在吸烟包年数< 5的受试者中未观察到（吸烟包年数=每天吸烟包数x吸烟年数）。进一步病例对照分析显示，OGG 1变异等位基因（Cys）与男性不育风险呈显性相关（OR = 1.35，95% CI：1.01-1.82;趋势P < 0.001）。此外，我们发现OGG 1 Ser 326 Cys多态性和吸烟与男性不育风险之间存在显着的基因-环境交互作用（P-interation = 0.0003）。这些发现提供了第一个证据，表明OGG 1多态性和吸烟对男性不育风险的潜在交互作用。(C)2013爱思唯尔爱尔兰有限公司版权所有。
8-Oxoguanine DNA glycosylase 1 (OGG1) plays an important role in repairing oxidative DNA damage induced by chemical agents, such as tobacco. This study examined the effects of OGG1 Ser326Cys polymorphism and cigarette smoking, alone or combined, on sperm oxidative DNA damage and the risk of male infertility. A total of 620 idiopathic infertile subjects and 480 fertile controls were recruited in this study. Sperm 8-hydroxydeoxyguanine (8-OHdG) was measured by immunofluorescent assay using flow cytometry and genotypes were determined by OpenArray platform with a chip-based Taq-Man genotyping technology. Our results demonstrated that both cigarette smoking and OGG1 polymorphism can affect the sperm 8-OHdG levels. Individuals with variant Cys/Cys homozygote showed higher levels of sperm 8-OHdG than wide-type homozygote carriers (Ser/Ser). Stratified analysis found that the association between OGG1 polymorphism and sperm 8-OHdG levels was only observed among smokers with pack-years >= 5 but not among those subjects with pack-years < 5 (pack-years = packs smoked per day x years as a smoker). Further analysis based on the case-control study revealed that variant allele (Cys) of OGG1 was significantly associated with male infertility risk in a dominant model (OR = 1.35, 95% CI: 1.01-1.82; trend P < 0.001). Furthermore, we found a significant gene-environment interaction between OGG1 Ser326Cys polymorphism and cigarette smoking in relation to male infertility risk (P-interation = 0.0003). These findings provided the first evidence about potential interactive effects of OGG1 polymorphism and cigarette smoking on male infertility risk. (C) 2013 Elsevier Ireland Ltd. All rights reserved.