| Objective To study the effect of six SNPs in DNA damage repair genes (hOGG1rs1052133;MUTYH rs3219489and rs10527342; ERCC5rs17655; RNF8rs2269058and rs761737) onsperm DNA integrity and primary male infertility. The effects of interactions between geneand gene or gene and environment on primary male infertility were also performed to clarifythe genetic etiology of male infertility.Methods332cases of primary male infertile patients were recruited from reproductivemedicine centre of general hospital of Ningxia Medical University, which includes in87casesof azoospermia,166cases of oligoasthenospermia and79cases of normozoospermia.329cases of fertile men taking a physical examination in the same hospital and fathered at leastone child in the absence of assistant reproductive technology were recruited as control.2mLof peripheral blood was drawn from both cases and controls; an extra2mL semen sample wasgiven by the cases and67cases of fertile men. Sperm DNA integrity and genotypes of sixSNPs were detected with the help of Sperm Chromatin Dispersion test (SCD) and PolymeraseChain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP), respectively. T testand Variance analysis were used to analyze the difference of sperm DFI between primarymale infertility and subgroups and control, respectively. Variance analysis was used to analyzethe difference of sperm DFI of three genotypes of the six SNPs in the case. The difference ofgenotype frequencies distribution of six SNPs between case and control were analyzed byusing Chi-square test. Logistic regression was performed to determine the risks of each SNP.Multifactor dimensionality reduction (MDR) and stratify analysis were used to analyze theassociations of gene-gene and gene-environment (alcohol consumption and cigarette smoking) interactions with the risk of primary male infertility, respectively.Results1. The sperm DFI of primary male infertility (46.2±22.3%) was significant higher than thatof fertile men (21.4±9.2%)(p<0.05). Analysis after stratified by primary male infertilesubgroups, the results suggest that sperm DFI in oligoasthenospermia group (50.0±22.1%)and normozoospermia group (38.2±20.7%) were significant higher than that of controlgroup (p<0.05). The sperm DFI in oligoasthenospermia was also significant higher thanthat of normozoospermia in primary male infertile group (p<0.05).2. The genotype frequencies distribution of hOGG1rs1052133(C→G) between primarymale infertility and control were significant (p<0.05), compared with CC genotype, theCG and GG genotype decrease the risk of male infertility(OR=0.54，95%CI=0.33-0.89；OR=0.55，95%CI=0.33-0.91, respectively). While other five SNPs were not associatedwith primary male infertility.3. There were no associations between SNPs and sperm DFI in the case group (p>0.05).4. Analysis after stratified by primary male infertile subgroups, the results revealed that:1) Rs1052133(C→G) in hOGG1was associated with oligoasthenospermia, comparedwith CC genotype, the CG and GG genotype decreased the risk of maleinfertility(OR=0.40，95%CI=0.22-0.70；OR=0.52，95%CI=0.29-0.92, respectively).2) The TT, CT and CC genotype frequencies distribution difference of RNF8rs761737(T→C) among azoospermia, oligoasthenospermia and normozoospermia group were notsignificant, but the risk of CT+CC genotype carriers was0.52fold than that of TTgenotype in normozoospermia in a dominant genetic model (P<0.05， OR=0.52，95%CI=0.28-0.97).3) The GG, CG and CC genotype frequencies distribution difference of MUTYHrs3219489(G→C) were significant between normozoospermia and control. Comparedwith the GG genotype，the CG and CC genotypes show significant associations with a decreased risk of normozoospermia (OR=0.56，95%CI：0.33-0.95；OR=0.32，95%CI：0.13-0.81, respectively). Meanwhile, the risk of individuals who carry CG+CCgenotype was0.50fold than that of GG genotype in a dominant genetic model(P<0.05，OR=0.50，95%CI：0.30-0.82). The G and C allele frequencies distributionwas significant difference between normozoospermia and control group, the risk ofindividuals who carry C allele was0.56fold than that of GG genotype (P<0.05，OR=0.56，95%CI：0.38-0.82).5. There are no gene-gene interactions among six SNPs on primary male infertility.6. The gene-environment interaction analysis reveals that there is a multiplied interactionbetween rs2269058and cigarette smoking, while no interactions between other SNPs andcigarette smoking or alcohol consumption were found.Conclusions1. Sperm DNA integrity in primary male infertility was decreased, but SNPs in hOGG1(rs1052133), MUTYH (rs3219489and rs10527342), RNF8(rs761737and rs2269058) andERCC5(rs17655) were not associated with sperm DFI.2. The CG and GG genotype of hOGG1rs1052133maybe protective factors ofoligoasthenospermia, while the C allele of MUTYH rs3219489maybe a protective factorof normozoospermia.3. The CT+CC genotype of RNF8rs761737maybe a protective factor of normozoospermiain a dominant model.4. ERCC5rs17655, MUTYH rs10527342and RNF8rs2269058maybe not associated withthe risk of primary male infertility.5. There are no interactions among six SNPs on primary male infertility, but there is aninteraction between RNF8rs2269058and cigarette smoking although it was not associatedwith sperm DNA integrity. |
