Il-1� C376a transversion variant and risk of idiopathic male infertility in Iranian men: A genetic association study

Background: 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. Materials and Methods: 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. Results: 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. Conclusion: 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. Keywords: Genetic Polymorphism, Interleukin-1α, Male Infertility, Spermatogenesi

Association of C3953T transition in interleukin 1β gene with idiopathic male infertility in an Iranian population

In this study we investigate the association of C3953T transition single nucleotide polymorphism in the fifth exon of the interleukin 1β gene with idiopathic male infertility. In a case-control study, blood samples were collected from 230 fertile and 207 infertile men who referred to the Kashan IVF centre. Genotypes of samples at the C3953T location were determined by polymerase chain reaction-restriction fragment length polymorphism. The data showed a significant association of TT genotype (OR = 2.49, 95CI = 1.02�6.10; p = 0.0452) and T allele (OR = 1.46, 95CI = 1.07�1.99; p = 0.0174) with male infertility. In a subgroup analysis, we found that the TT genotype (OR = 3.28, 95CI = 1.16�9.26; p = 0.0249) and T allele (OR = 1.63, 95CI = 1.10�2.41; p = 0.0142) were associated with oligozoospermia. Our findings suggest that the C3953T polymorphism could be considered as a potential biomarker for a genetic diagnosis of male infertility. © 2017, © 2017 The British Fertility Society

IL-1RA VNTR and IL-1α 4845G>T polymorphisms and risk of idiopathic male infertility in Iranian men: A case�control study and an in silico analysis

Abstract 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