Department of Molecular and Cell Biology, Faculty of Basic Sciences, University of Mazandaran, Babolsar, Mazandaran, Post Code: 47416-95447, Iran.
Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, P.O. Box: 14395-1561, Tehran, Iran.
Environ Sci Pollut Res Int. 2017 Sep;24(25):20599-20615. doi: 10.1007/s11356-017-9701-2. Epub 2017 Jul 15.
Aryl hydrocarbon receptor (AHR) is responsible for crucial events in male reproductive biology. Here, the association of the AHR transitions c.-742C>T and c.1661G>A with idiopathic male infertility was investigated in a case-control study, which is followed by a meta-analysis and a bioinformatic investigation. Blood and semen samples were obtained from a total of 135 idiopathic infertile men and 130 healthy controls. Participants were genotyped for the transitions using a PCR-RFLP method. A meta-analysis of five sets of data evaluated the association of c.1661G>A with male infertility, and using an in silico analysis, the possible molecular effects of the transitions predicted. Genotypes and alleles of AHR-c.-742C>T and c.1661G>A polymorphisms were not associated with the risk of male infertility significantly. However, the frequency of C/A haplotype was significantly associated with the increased risk of male infertility, and T/A haplotype was higher among controls significantly. Also, the frequencies of combined genotypes CT/GG, CT/GA and TT/GG were significantly associated with decreased risk of infertility. And, the meta-analysis showed that the AA versus GA/GG recessive model is associated with decreased risk of male infertility among the Iranian population. In silico analysis predicted that c.-742C>T does not alter the binding sites of the proposed transcription factors, but c.1661G>A poses a tolerable structural disturbance in AHR protein. In conclusion, these results showed that AHR c.-742C>T and c.1661G>A transitions separately could not be nominated as a risk or protective factor for male infertility. However, some combined models could affect infertility risk, especially among Iranian men.
芳香烃受体 (AHR) 在男性生殖生物学中起着至关重要的作用。在这里，我们通过病例对照研究调查了 AHR 突变 c.-742C>T 和 c.1661G>A 与特发性男性不育之间的关联，随后进行了荟萃分析和生物信息学研究。我们从 135 名特发性不育男性和 130 名健康对照中获得了血液和精液样本。使用 PCR-RFLP 方法对这些突变进行了基因分型。荟萃分析了五组数据，评估了 c.1661G>A 与男性不育之间的关联，并通过计算机模拟分析预测了这些突变的可能分子效应。AHR-c.-742C>T 和 c.1661G>A 多态性的基因型和等位基因与男性不育的风险没有显著关联。然而，C/A 单倍型的频率与男性不育的风险增加显著相关，而 T/A 单倍型在对照组中显著更高。此外，CT/GG、CT/GA 和 TT/GG 联合基因型的频率与不育风险降低显著相关。荟萃分析表明，在伊朗人群中，AA 与 GA/GG 隐性模型与男性不育风险降低相关。计算机模拟分析预测，c.-742C>T 不会改变拟议转录因子的结合位点，但 c.1661G>A 会导致 AHR 蛋白的结构干扰。总之，这些结果表明，AHR c.-742C>T 和 c.1661G>A 突变单独不能作为男性不育的风险或保护因素。然而，一些联合模型可能会影响不育风险，尤其是在伊朗男性中。
