Department of Molecular and Cell Biology, Faculty of Basic Sciences, University of Mazandaran, Babolsar, 47416-95447, Iran.
Cellular and Molecular Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.
J Assist Reprod Genet. 2017 Dec;34(12):1673-1682. doi: 10.1007/s10815-017-1033-0. Epub 2017 Sep 20.
In this study, we evaluate the relationship between genetic polymorphisms of the DJ-1 gene, g.-6_+10del, and g.168_185del with male infertility susceptibility.
Four hundred and twenty-two male infertile patients and 285 fertile male controls were recruited. Genotyping was performed by polymerase chain reaction. In silico analysis was performed by EPD, ElemeNT, SNPnexus, and PROMO to predict the potential functions of rs901561484 and rs373653682 polymorphisms.
The Del (D) allele carriers of DJ-1 g.-6_+10del polymorphism were significantly associated with the risk of male infertility in total infertile, asthenozoospermia, and oligoasthenozoospermia patients. Moreover, the Del (D) allele of DJ-1 g.-6_+10del polymorphism significantly increased in total male infertile, asthenozoospermia, and oligoasthenozoospermia groups. In addition, the frequencies of different genotypes and the Del allele and Dup allele carriers of DJ-1 g.168_185del gene polymorphisms were associated with male infertility in total infertile and four different sub-group patients. Furthermore, haplotype analysis of DJ-1 g.-6_+10del and g.168_185del polymorphisms revealed that the D-Dup and I-Del haplotype frequencies significantly increased the risk of male infertility, while I-Ins haplotypes were associated with a decreased risk of male infertility in total and sub-group patients. The in silico analysis showed that the presence of Ins and/or Dup alleles of the DJ-1 g.-6_+10del and g.168_185del polymorphisms could provide additional binding sites of more nuclear factors and probably affect transcriptional activity.
CONCLUSION(S): Our study presents evidence of a strong association between functional polymorphisms of the DJ-1 promoter, g.-6_+10del, and g.168_185del with the risk of male infertility.
本研究旨在评估 DJ-1 基因 g.-6_+10del 和 g.168_185del 遗传多态性与男性不育易感性之间的关系。
招募了 422 名男性不育患者和 285 名正常生育男性作为对照组。采用聚合酶链反应进行基因分型。通过 EPD、ElemeNT、SNPnexus 和 PROMO 进行的计算机分析，预测 rs901561484 和 rs373653682 多态性的潜在功能。
DJ-1 g.-6_+10del 多态性的 Del(D)等位基因携带者与总不育、弱精症和少弱精症患者的男性不育风险显著相关。此外，DJ-1 g.-6_+10del 多态性的 Del(D)等位基因在总不育、弱精症和少弱精症组中显著增加。此外，DJ-1 g.168_185del 基因多态性的不同基因型和 Del 等位基因和 Dup 等位基因携带者频率与总不育和四个不同亚组患者的男性不育有关。此外，DJ-1 g.-6_+10del 和 g.168_185del 多态性的单体型分析表明，D-Dup 和 I-Del 单体型频率显著增加了男性不育的风险，而 I-Ins 单体型与总人群和亚组患者的男性不育风险降低有关。计算机分析表明，DJ-1 g.-6_+10del 和 g.168_185del 多态性的 Ins 和/或 Dup 等位基因的存在可以提供更多核因子的额外结合位点，并可能影响转录活性。
本研究提供了强有力的证据表明，DJ-1 启动子的功能多态性 g.-6_+10del 和 g.168_185del 与男性不育的风险密切相关。
