State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China.
Free Radic Biol Med. 2012 Feb 15;52(4):775-80. doi: 10.1016/j.freeradbiomed.2011.11.032. Epub 2011 Dec 21.
To test the hypothesis that polymorphisms in antioxidant genes are more susceptible to sperm DNA damage and male infertility, we examined 11 single-nucleotide polymorphisms from six antioxidant genes (GPX1, CAT, PON1, NQO1, SOD2/MnSOD, and SOD3) in 580 infertility cases and 580 controls from a Chinese population-based case-control study (NJMU Infertility Study). Genotypes were determined using the OpenArray platform. Sperm DNA fragmentation was detected using the Tdt-mediated dUTP nick-end labeling assay, and the level of 8-hydroxydeoxyguanosine (8-OHdG) in sperm DNA was measured using immunofluorescence. The adjusted odds ratio and 95% confidence interval (CI) were estimated using unconditional logistic regression. The results indicated that the PON1 Arg192Glu (rs662) and SOD2 Val16Ala (rs4880) variant genotypes were associated with a significantly higher risk of male infertility. In addition, subjects carrying variant genotypes of both loci had a twofold (95% CI, 1.42-2.90) increase in the risk of male infertility, indicating a significant gene-gene interaction between these two loci (P for multiplicative interaction=0.045). Moreover, linear regression analysis showed that individuals carrying the PON1 Arg192Glu (rs662) or SOD2 Val16Ala (rs4880) variants have significantly higher levels of sperm DNA fragmentation and 8-OHdG. These data suggest that genetic variations in antioxidant genes may contribute to oxidative sperm DNA damage and male infertility.
为了验证抗氧化基因多态性更容易导致精子 DNA 损伤和男性不育的假设，我们在中国人群病例对照研究（南京医科大学不育研究）中，对来自 6 个抗氧化基因（GPX1、CAT、PON1、NQO1、SOD2/MnSOD 和 SOD3）的 11 个单核苷酸多态性（SNP），在 580 例不育病例和 580 例对照中进行了检测。使用 OpenArray 平台确定基因型。使用 Tdt 介导的 dUTP 缺口末端标记（TUNEL）检测精子 DNA 碎片化，使用免疫荧光法测量精子 DNA 中的 8-羟基脱氧鸟苷（8-OHdG）水平。使用非条件逻辑回归估计调整后的比值比和 95％置信区间（CI）。结果表明，PON1Arg192Glu（rs662）和 SOD2Val16Ala（rs4880）变异基因型与男性不育的风险显著增加相关。此外，携带这两个位点变异基因型的受试者，男性不育的风险增加了两倍（95％CI，1.42-2.90），表明这两个位点之间存在显著的基因-基因相互作用（P 值为乘法交互作用=0.045）。此外，线性回归分析表明，携带 PON1Arg192Glu（rs662）或 SOD2Val16Ala（rs4880）变异的个体，精子 DNA 碎片化和 8-OHdG 的水平显著升高。这些数据表明，抗氧化基因中的遗传变异可能导致氧化应激导致的精子 DNA 损伤和男性不育。
