Ghasemi Hadi, Khodadadi Iraj, Fattahi Amir, Moghimbeigi Abbas, Tavilani Heidar
a Department of Biochemistry , Hamadan University of Medical Sciences , Hamadan , Iran.
b Women's Reproductive Health Research Center , Tabriz University of Medical Sciences , Tabriz , Iran.
Syst Biol Reprod Med. 2017 Dec;63(6):382-390. doi: 10.1080/19396368.2017.1374488. Epub 2017 Oct 9.
Sperm DNA damage is one of the associated factors of idiopathic male infertility and abnormal spermatogenesis. This study was conducted to assess possible association between risk of male infertility with X-ray repair cross complementing group 1 (XRCC1) Arg399Gln (G to A) and DNA ligase 4 (LIG4) Thr9Ile (C to T) gene polymorphisms which are involved in different DNA repair pathways. In this case-control study 191 fertile and 191 infertile men (29-40 years old) were enrolled. The single-nucleotide polymorphism genotypes and alleles of XRCC1 Arg399Gln and LIG4 Thr9Ile were assessed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. There was no significant association between XRCC1 Arg399Gln polymorphism and risk of male infertility. The frequency of LIG4 Thr9Ile genotypes and alleles were statistically different between fertile and infertile men (p<0.001). We found that the CT genotype increased infertility risk more than threefold (OR, 3.12; 95% CI, 1.803-5.407). The LIG4 TT genotype carriers had decreased progressive motile sperm (p<0.05) and increased non-progressive motile sperm (p<0.001) compared with the CC genotype. Moreover, sperm concentration in subjects carrying the CT genotype was lower than that observed in CC carriers (p<0.05). The results revealed that the GG/CT and GA/CT combinations of genotypes increase the risk of infertility 3.5 and fourfold, respectively (p=0.021 and 0.004, respectively). This study demonstrated that there was an association between LIG4 Thr9Ile polymorphism and male infertility and suggests CT genotype as a risk factor for male infertility.
精子DNA损伤是特发性男性不育症和精子发生异常的相关因素之一。本研究旨在评估男性不育风险与参与不同DNA修复途径的X射线修复交叉互补组1（XRCC1）Arg399Gln（G到A）和DNA连接酶4（LIG4）Thr9Ile（C到T）基因多态性之间的可能关联。在这项病例对照研究中，纳入了191名生育能力正常的男性和191名不育男性（年龄在29至40岁之间）。使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术评估XRCC1 Arg399Gln和LIG4 Thr9Ile的单核苷酸多态性基因型和等位基因。XRCC1 Arg399Gln多态性与男性不育风险之间没有显著关联。生育能力正常和不育男性之间LIG4 Thr9Ile基因型和等位基因的频率在统计学上存在差异（p<0.001）。我们发现CT基因型使不育风险增加了三倍多（比值比，3.12；95%置信区间，1.803-5.407）。与CC基因型相比，LIG4 TT基因型携带者的进行性运动精子减少（p<0.05），非进行性运动精子增加（p<0.001）。此外，携带CT基因型的受试者的精子浓度低于CC携带者（p<0.05）。结果显示，GG/CT和GA/CT基因型组合分别使不育风险增加3.5倍和四倍（p分别为0.021和0.004）。本研究表明LIG4 Thr9Ile多态性与男性不育之间存在关联，并提示CT基因型是男性不育的一个风险因素。
