MTHFR-Ala222Val and male infertility: a study in Iranian men, an updated meta-analysis and an in silico-analysis

Nikzad, Hossein; Karimian, Mohammad; Sareban, Kobra; Khoshsokhan, Maryam; Colagar, Abasalt Hosseinzadeh

doi:10.1016/j.rbmo.2015.07.015

Cited by 34 publications

(22 citation statements)

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“…While in vitro and in vivo analyses are useful for detecting the effects of polymorphisms on molecular aspects of the origin gene, they are costly and time consuming. Computational analysis is a more useful and low‐cost way to evaluate mutational analysis (Ebrahimi, Colagar, & Karimian, ; Karimian et al, ; Nikzad et al, ). Therefore, in this study we used bioinformatics software for analysing the molecular effects of IL‐1RA VNTR, and IL‐1α 4845G>T polymorphisms.…”

Section: Discussionmentioning

confidence: 99%

“…Single nucleotide polymorphisms (SNPs), as common genetic variations, can affect gene expression, mRNA structure and protein function resulting in male infertility (Karimian & Hosseinzadeh Colagar, ; Nikzad, Karimian, Sareban, Khoshsokhan, & Colagar, ; Zamani‐Badi, Karimian, Azami Tameh, & Nikzad, ). There are VNTR (ID: rs2234663) and 4845G>T (ID: rs17561) common polymorphisms in IL‐1RA and IL‐1α genes respectively.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

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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“…Male infertility has been a rapidly developing area of medical science. Great interest has been raised by novel insight on numerous of male infertility, including pathogenesis, personalized therapeutic protocols, molecular changes and social effects (Nikzad et al ., ). An increasing number of journals have appeared dealing with male infertility medicine, and the total number of published articles has grown each year.…”

Section: Introductionmentioning

confidence: 97%

Research trends and perspectives of male infertility: a bibliometric analysis of 20 years of scientific literature

Zhang

Xiao

et al. 2016

Andrology

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To carry out an in-depth analysis of the scientific research on male infertility, we performed the first bibliometric analysis focusing on studies involving male infertility worldwide during the period 1995-2014. Analysis of 6357 articles in the field of male infertility showed a significant increasing trend in the number of publications over the period 1995-2014. Obstetrics and Gynecology was an important subject category and Multidisciplinary Sciences was the newest interest. Authors were mainly from Europe and USA, with researchers from Cleveland Clinic producing the most articles, and those from the Tel Aviv Sourasky Medical Center and the University of Utah having the highest-quality articles. The USA contributed the most independent and international collaborative articles. The Cleveland Clinic and the University of Munster were the most productive institutions. The Cleveland Clinic and the University of Giessen had the most international collaboration publications. Harvard University had the most collaborators. The most common interests were pathogenesis and therapy, and new interests were hypogonadism, obesity, and cryopreservation. In conclusion, rapid development of the male infertility field was observed. Overall, collaborative and multidisciplinary science research has become more popular. The USA and its institutions play a dominant role, followed by European countries. Thanks to the common research focus worldwide, more insight into male fertility has been gained in the scientific literature over the past 20 years. [Correction added on September 21, 2016, after online publication: the term "institute" has been replaced by the term "institution" throughout the text.].

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“…The single nucleotide polymorphisms (SNPs) of these folate-related enzymes gene can impair folate absorption or disturb the balance between folate derivatives by impacting the activity, stability, or level of the corresponding enzymes. The mechanisms of pathogenesis may involve changes of enzyme structure and mRNA properties that are due to these folate-related enzymes gene polymorphisms[28]. Recent studies have revealed that folate-related enzyme gene polymorphisms were associated with an increased risk of male infertility, particularly in the case of MTHFR gene polymorphisms[1, 29, 30].…”

Section: Discussionmentioning

confidence: 99%

MTHFR C677T, A1298C and MS A2756G Gene Polymorphisms and Male Infertility Risk in a Chinese Population: A Meta-Analysis

Ren

Yang

et al. 2017

PLoS ONE

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BackgroundMethylenetetrahydrofolate reductase gene (MTHFR C677T and A1298C) and methionine synthase gene (MS A2756G) polymorphisms have shown an association with male infertility risk in several ethnic populations. Although several studies have evaluated these associations in Chinese populations, their small sample sizes and inconsistent outcomes have prevented strong conclusions. Therefore, the present meta-analysis was performed with published studies to evaluate the associations of the three single nucleotide polymorphisms (SNPs) and male infertility in a Chinese population.MethodsWe conducted a search of PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI), China biology medical literature (CBM), VIP, and Chinese literature (Wan Fang) databases up to May 31, 2016. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were used to assess the strength of associations with a random-effect model or a fixed-effect model based on the heterogeneity analysis results. Sensitivity analysis was used to confirm the reliability and stability of the meta-analysis.ResultsA total of nine studies, including 1,713 cases and 1,104 controls, were included in the meta-analysis. The pooled results indicated that the MTHFR C667T polymorphism was significantly associated with increased risk of male infertility in the Chinese population in the allele model (T vs. C: OR = 1.47, 95%CI = 1.32–1.63), the dominant model (TT + CT vs. CC: OR = 1.51, 95%CI = 1.30–1.77), the additive model (TT vs. CC: OR = 2.08, 95%CI = 1.68–2.58) and the recessive model (TT vs. CT+CC: OR = 1.58, 95%CI = 1.31–1.90), whereas the MTHFR A1298C and MS A2756G polymorphisms were not risk factors. There was no significant heterogeneity in any genotype contrasts among the studies. The sensitivity analysis indicated that the results of this meta-analysis were relatively stable.ConclusionThis study suggests that the MTHFR C667T polymorphism may contribute to the genetic susceptibility to male infertility in the Chinese population, whereas MTHFR A1298C and MS A2756G polymorphisms may be unrelated to male infertility. Studies with larger sample sizes and representative population-based cases and well-matched controls are needed to validate our results.

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MTHFR-Ala222Val and male infertility: a study in Iranian men, an updated meta-analysis and an in silico-analysis

Cited by 34 publications

References 70 publications

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

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

Research trends and perspectives of male infertility: a bibliometric analysis of 20 years of scientific literature

MTHFR C677T, A1298C and MS A2756G Gene Polymorphisms and Male Infertility Risk in a Chinese Population: A Meta-Analysis

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