Genetic variants in antioxidant genes are associated with sperm DNA damage and risk of male infertility in a Chinese population.
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.
State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China.
Guixiang
G
Ji
Aihua
A
Gu
Yubang
Y
Wang
Cong
C
Huang
Fan
F
Hu
Yong
Y
Zhou
Ling
L
Song
Xinru
X
Wang
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D043303:Aryldialkylphosphatase / Q000235:genetics*; D016022:Case-Control Studies; D002374:Catalase / Q000235:genetics; D002681:China; D053938:DNA Fragmentation; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004843:Epistasis, Genetic; D056726:Genetic Association Studies; D005838:Genotype; D005979:Glutathione Peroxidase / Q000235:genetics; D006801:Humans; D007248:Infertility, Male / Q000201:enzymology / Q000209:etiology / Q000235:genetics*; D008297:Male; D018384:Oxidative Stress / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D012907:Smoking / Q000009:adverse effects; D013094:Spermatozoa / Q000201:enzymology* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics*; D000094765:Glutathione Peroxidase GPX1; D000099156:Superoxide Dismutase 2
D000080242:8-Hydroxy-2'-Deoxyguanosine; D043303:Aryldialkylphosphatase; D002374:Catalase; D003849:Deoxyguanosine; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000094765:Glutathione Peroxidase GPX1; D000099156:Superoxide Dismutase 2; C441642:SOD3 protein, human; C468406:PON1 protein, human; C000722067:GPX1 protein, human