Significant association of TNFα and IL-6 gene with male infertility—An explorative study in Indian populations of Uttar Pradesh

Shukla, Kamla Kant; Agnihotri, Shalini; Gupta, Abhishek; Mahdi, Abbas Ali; Elsayed, Mohamed; Sankhwar, Satya Narayan; Sharma, Praveen

doi:10.1016/j.imlet.2013.08.011

Cited by 20 publications

(13 citation statements)

References 27 publications

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“…i.e. substitution level from G to A in the TNF-α gene was significantly higher in the infertile subjects as compared to fertile controls 18 . Likewise, Egyptian population report by Zalata et al documented significant overrepresentation of TNF -308AA carriers among patients diagnosed with asthenozoospermia, asthenoteratozoospermia and oligoasthenoteratozoospermia 19 .…”

Section: Discussionmentioning

confidence: 81%

TGFβ3 (TGFB3) polymorphism is associated with male infertility

Droździk

Kaczmarek

Malinowski

et al. 2015

Sci Rep

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Factors affecting the blood-testis barrier function may be involved in testicular damage and male infertility. Two cytokines play an important role in the barrier regulation, namely transforming growth factor beta 3 (TGF-β3) and tumor necrosis factor (TNF-α). The aim of this study was to investigate the potential association between TGF-β3 (TGFB3) and TNF-α (TNF) gene polymorphisms and male infertility. A total of 846 subjects, 423 diagnosed with male infertility and 423 fertile men were enrolled. TGFB3 (rs2268626:T > C, rs3917158:C > T, rs2284792:A > G, rs2268625:T > C, rs3917187:C > T) and TNF (rs1800629:-308G > A) gene polymorphisms were genotyped. No association between TNF genotype and infertility was observed. As for TGFB3, the genotypes distribution was similar in infertile and fertile men. However, rs2284792 minor allele frequency was significantly higher among infertile subjects. Heterozygous rs2284792 AG genotype was associated with increased odds for infertility [OR = 1.40 (95% CI 1.05–1.86), p = 0.021] and similar results were observed for G allele carrier status [OR = 1.40 (95% CI 1.06–1.84), p = 0.017]. Heterozygosity in TGFB3 rs3917158 was also associated with the infertility [OR = 1.37 (95% CI 1.01–1.87), p = 0.041]. The TGFB3 variant genotypes were associated with lower spermatozoa motility parameters in fertile men. The results indicate that variants in TGFB3 gene may be associated with male infertility. However, the findings require further replication and validation.

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Section: Discussionmentioning

confidence: 81%

TGFβ3 (TGFB3) polymorphism is associated with male infertility

Droździk

Kaczmarek

Malinowski

et al. 2015

Sci Rep

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“…Infertility affects approximately 15% of couples, with male factor infertility accounting for 50% of infertile couples (Agarwal & Said, ; Shukla et al, ). In more than 70% of cases, etiologies of male infertility have been identified as endocrine disruptors, varicocele, infectious diseases, post‐testicular obstruction, aneuploidies etc.…”

Section: Introductionmentioning

confidence: 99%

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

2018

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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.

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“…However, when considering the rest of the world, the IL6 À174G frequency displayed a positive correlation with fertility (r 74 = 0.741) and, at the same time, with child mortality rate (r 74 = 0.674). Notably, several studies reported the association of IL6 À174C allele both with abortion (von Linsingen et al, 2005;Demirturk et al, 2014) and male infertility (Shukla et al, 2013). Moreover, the increased fertility associated with IL6 À174G frequency turned out to be counterbalanced by a reduced lifeexpectancy (r 2 = À0.720).…”

Section: Discussionmentioning

confidence: 99%