Zamani-Badi Tayyebeh, Karimian Mohammad, Azami Tameh Abolfazl, Nikzad Hossein
Gametogenesis Research Center, Kashan University of Medical Sciences, Kashan, Iran.
Anatomical Sciences Research Center, Kashan University of Medical Sciences, Kashan, Iran.
Int J Fertil Steril. 2018 Jun;12(3):229-234. doi: 10.22074/ijfs.2018.5375. Epub 2018 Jun 20.
IL-1α produced by Sertoli cells is considered to act as a growth factor for spermatogonia. In this study, we investigated the association of the C376A polymorphism in IL-1α with male infertility in men referring to the Kashan IVF Center.
In this case-control study, 2 ml of blood was collected from 230 fertile and 230 infertile men. After DNA extraction, the C376A variant was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In addition, the molecular effects of the C376A transversion were analysed using bioinformatics tools.
A significant association was observed between the homozygous genotype CC with male infertility [odds ratio (OR)=1.97, 95% confidence interval (CI)=1.14-3.41, P=0.016)]. Carriers of C (AC+CC) showed a similar risk for male infertility (OR=1.78, 95% CI=1.06-2.99, P=0.030). Also, allelic analysis showed that the C allele is associated with male infertility (OR=1.43, 95% CI=1.09-1.88, P=0.011). In sub-group analysis, we found that the AC genotype is associated with asthenozoospermia (OR=2.38, 95% CI=1.03-5.53, P=0.043). In addition, carriers of C were at high risk for asthenozoospermia (OR=2.25, 95% CI=1.01-4.10, P=0.047). Also, C allele was significantly associated with oligozoospermia (OR=1.44, 95% CI=1.01-2.06, P=0.049) and non-obstructive azoospermia (OR=1.67, 95% CI =1.04-2.68, P=0.034). Finally, in silico analysis showed that the C376A polymorphism could alter splicing especially in the acceptor site.
This is the preliminary report on the association of IL-1α C376A polymorphism with male infertility in the Kashan population. This association shows that the IL-1α gene may be a biomarker for male infertility, and therefore needs additional investigations in future studies to validate this.
支持细胞产生的白细胞介素-1α（IL-1α）被认为是精原细胞的生长因子。在本研究中，我们调查了伊朗卡尚体外受精中心男性中IL-1α基因C376A多态性与男性不育的关联。
在这项病例对照研究中，采集了230名生育力正常男性和230名不育男性的2毫升血液。DNA提取后，采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）对C376A变异进行基因分型。此外，使用生物信息学工具分析了C376A转换的分子效应。
观察到纯合基因型CC与男性不育之间存在显著关联[优势比（OR）=1.97，95%置信区间（CI）=1.14 - 3.41，P = 0.016]。C等位基因携带者（AC + CC）患男性不育的风险相似（OR = 1.78，95% CI = 1.06 - 2.99，P = 0.030）。此外，等位基因分析表明C等位基因与男性不育相关（OR = 1.43，95% CI = 1.09 - 1.88，P = 0.011）。在亚组分析中，我们发现AC基因型与弱精子症相关（OR = 2.38，95% CI = 1.03 - 5.53，P = 0.043）。此外，C等位基因携带者患弱精子症的风险较高（OR = 2.25，95% CI = 1.01 - 4.10，P = 0.047）。而且，C等位基因与少精子症（OR = 1.44，95% CI = 1.01 - 2.06，P = 0.049）和非梗阻性无精子症（OR = 1.67，95% CI = 1.04 - 2.68，P = 0.034）显著相关。最后，计算机模拟分析表明C376A多态性可能会改变剪接，尤其是在受体位点。
这是关于伊朗卡尚人群中IL-1α基因C376A多态性与男性不育关联的初步报告。这种关联表明IL-1α基因可能是男性不育的生物标志物，因此在未来的研究中需要进一步研究来验证这一点。
