Zamani-Badi Tayyebeh, Nikzad Hossein, Karimian Mohammad
Gametogenesis Research Center, Kashan University of Medical Sciences, Kashan, Iran.
Anatomical Sciences Research Center, Kashan University of Medical Sciences, Kashan, Iran.
Andrologia. 2018 Nov;50(9):e13081. doi: 10.1111/and.13081. Epub 2018 Jul 3.
This study aimed to investigate the association of IL-1RA VNTR and IL-1α 4845G>T polymorphisms with idiopathic male infertility followed by an in silico analysis. In a case-control study, we collected blood samples from 230 infertile and 230 healthy men. Genotyping of IL-1RA VNTR was performed by PCR whereas IL-1α 4845G>T was genotyped by polymerase chain reaction-restriction fragment length polymorphism. An in silico approach was employed for the detection of IL-1RA VNTR and IL-1α 4845G>T effects on some molecular aspects of IL-1RA and IL-1α respectively. The result of our genetic association study for IL-1α 4845G>T revealed that there was a significant association between GT genotype, TT genotype, T allele and idiopathic male infertility. Although there was no significant association between IL-1RA VNTR and male infertility in the overall analysis. However, subgroup analysis revealed that the subjects with VNTR 4R/5R genotype were at a higher risk of oligozoospermia. Furthermore, 4845TT genotype, and 4845T allele were associated with oligozoospermia, asthenozoospermia and nonobstructive azoospermia. Bioinformatics analysis showed that IL-1RA VNTR may affect the splicing pattern of IL-1RA. Moreover, IL-1α 4845G>T has a significant effect on RNA structure and protein function. Based on our findings, both IL-1RA VNTR and IL-1α 4845G>T polymorphisms could be considered as potential biomarkers for screening of susceptible individuals.
本研究旨在探讨白细胞介素-1受体拮抗剂（IL-1RA）可变数目串联重复序列（VNTR）和白细胞介素-1α（IL-1α）4845G>T多态性与特发性男性不育症的关联，并进行计算机模拟分析。在一项病例对照研究中，我们收集了230名不育男性和230名健康男性的血液样本。采用聚合酶链反应（PCR）对IL-1RA VNTR进行基因分型，而IL-1α 4845G>T则通过聚合酶链反应-限制性片段长度多态性进行基因分型。采用计算机模拟方法分别检测IL-1RA VNTR和IL-1α 4845G>T对IL-1RA和IL-1α某些分子层面的影响。我们对IL-1α 4845G>T的基因关联研究结果显示，GT基因型、TT基因型、T等位基因与特发性男性不育症之间存在显著关联。尽管在总体分析中IL-1RA VNTR与男性不育症之间无显著关联。然而，亚组分析显示，VNTR 4R/5R基因型的受试者少精子症风险较高。此外，4845TT基因型和4845T等位基因与少精子症、弱精子症和非梗阻性无精子症相关。生物信息学分析表明，IL-1RA VNTR可能影响IL-1RA的剪接模式。此外，IL-1α 4845G>T对RNA结构和蛋白质功能有显著影响。基于我们的研究结果，IL-1RA VNTR和IL-1α 4845G>T多态性均可被视为筛查易感个体的潜在生物标志物。
