Association between methionine synthase reductase A66G polymorphism and primary infertility in Chinese males

Li, X.Y.; Ye, J.Z.; Ding, Xianping; Zhang, X.H.; Ma, Tengjiao; Zhong, Rugang; Ren, Hongyan

doi:10.4238/2015.april.15.13

Cited by 12 publications

(6 citation statements)

References 36 publications

(54 reference statements)

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“…[15–36] 20 studies were concerned with the association between MTHFR C677T polymorphism and male infertility, [15–18,20,21,23–36] 12 studies evaluated the MTHFR A1298C polymorphism, [15–17,19,20,22,28,29,33,35,36] and only 4 studies evaluated the MTRR A66G polymorphism. [15,17,28,29] The main characteristics and quality score of each study were displayed in Table 1. All studies were stratified by geographical location, of which 14 studies were performed in East Asians [15,16,18,21,22,24–29,32–34] and the remaining 8 across South/West Asians.…”

Section: Resultsmentioning

confidence: 99%

“…[15,17,28,29] The main characteristics and quality score of each study were displayed in Table 1. All studies were stratified by geographical location, of which 14 studies were performed in East Asians [15,16,18,21,22,24–29,32–34] and the remaining 8 across South/West Asians. [17,19,20,23,30,31,35,36] When stratified by source of controls, the amount of hospital-based (HB) studies was 10, [17,18,21,25,28,30–32,35–36] population-based (PB) studies was 8, [19,22–24,27,29,33,34] and mixed population or uncertain source was 4.…”

Section: Resultsmentioning

confidence: 99%

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The relevance of MTHFR C677T, A1298C, and MTRR A66G polymorphisms with response to male infertility in Asians

Shi

Liu

et al. 2019

Medicine

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Although published studies have reported the association between MTHFR C677T (rs 1801133), A1298C (rs 1801131), and MTRR A66G (rs1801394) polymorphisms and male infertility in Asian populations, the results are conflicting. In order to accurately evaluate the relevance, a meta-analysis was performed. We searched for potential studies in 4 databases, containing PubMed, ScienceDirect, China National Knowledge Infrastructure (CNKI), and Wanfang database until May 31, 2018. The summarized odds ratio (OR) with 95% confidence intervals (95% CI) were calculated to evaluate the relevance in 5 genetic models. The heterogeneity test, sensitivity analysis, and publication bias test was performed by Review Manager 5.3 software. Overall, 22 case–control studies with 5049 cases and 4157 controls were included in this meta-analysis, which contained 20 studies of MTHFR C677T polymorphism, 12 studies of MTHFR A1298C polymorphism and 4 studies of MTRR A66G polymorphism. The results indicated that MTHFR C677T, A1298C, and MTRR A66G polymorphisms were significantly associated with male infertility in Asian populations (Dominant model: MTHFR CC + CT vs TT: OR = 0.60, 95% CI (0.53, 0.67), P <.00001; MTHFR AA + AC vs CC: OR = 0.62, 95% CI (0.49, 0.79), P = .0001; MTRR AA + AG vs GG: OR = 0.60, 95% CI (0.45, 0.81), P = .001. Recessive model: MTHFR CC vs CT + TT: OR = 0.67, 95% CI (0.61, 0.74), P <.00001; MTHFR AA vs AC + CC: OR = 0.79, 95% CI (0.70, 0.88), P <.0001; MTRR AA vs AG + GG: OR = 0.70, 95% CI (0.56, 0.88), P = .002. Heterozygote model: MTHFR CC vs CT: OR = 0.74, 95% CI (0.67, 0.82), P <.00001; MTHFR AA vs AC: OR = 0.83, 95% CI (0.73, 0.93), P = .002; MTRR AA vs AG: OR = 0.76, 95% CI (0.60, 0.92), P = .02. Homozygote model: MTHFR CC vs TT: OR = 0.48, 95% CI (0.41, 0.56), P <.00001; MTHFR AA vs CC: OR = 0.61, 95% CI (0.39, 0.93), P = .02; MTRR AA vs GG: OR = 0.51, 95% CI (0.36, 0.72), P = .0001. Allele model: MTHFR C vs T: OR = 0.70, 95% CI (0.66, 0.75), P <.00001; MTHFR A vsC: OR = 0.82, 95% CI (0.71, 0.95), P = .01; MTRR A vs G: OR = 0.76, 95% CI (0.66, 0.88), P = .00003). Stratified analyses by geographical location and source of controls showed the same results. Sensitivity analyses indicated that the final consequences of this meta-analysis were stable, and the publication biases test had not found obvious asymmetry. This meta-analysis indicates that MTHFR C677T, A1298C, and MTRR A66G polymorphisms are the risk factors with susceptibility to male infertility in Asians.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

The relevance of MTHFR C677T, A1298C, and MTRR A66G polymorphisms with response to male infertility in Asians

Shi

Liu

et al. 2019

Medicine

View full text Add to dashboard Cite

show abstract

“…Two additional eligible studies [30,31] were identified by searching the references of original articles and review articles. In total, 20 articles [11,[30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48] involving 4293 cases and 4507 controls were included in this meta-analysis based on the inclusion and exclusion criteria. Table 1 lists the main characteristics of the included studies.…”

Section: Study Characteristicsmentioning

confidence: 99%

Association between MTHFR A1298C polymorphism and male infertility: A meta-analysis

Zhang

Yin

Liu

et al. 2017

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

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There have been several epidemiological studies evaluating the potential association between the methylenetetrahydrofolate reductase (MTHFR) A1298C polymorphism and the risk of male infertility. However, the results obtained were inconsistent. Therefore, we performed a meta-analysis to further examine the association between the MTHFR A1298C polymorphism and male infertility. A comprehensive search was conducted to identify all eligible studies from the online literature databases published prior to January 15th, 2016. A total of 20 studies with 4293 cases and 4507 controls were included. An odds ratio (OR) and a 95% confidence interval (95% CI) were calculated to assess the strength of the association. A cumulative meta-analysis, sensitivity analysis and assessment of the publication bias were also performed in this study. The results showed that in the overall analysis, the association between the MTHFR A1298C polymorphism and male infertility was not significant. A stratified analysis by ethnicity revealed a significant increase in the risk of male infertility in the Asian population with the MTHFR A1298C polymorphism (especially in the heterozygote model: OR=1.20, 95% CI=1.01-1.44, P=0.994; the dominant model: OR=1.23, 95% CI=1.04-1.45, P=0.996; and the allele model: OR=1.20, 95% CI=1.04-1.39, P=0.985) but not in the Caucasian population. In the stratified analyses, no significant association was observed between the different types of male infertility. This meta-analysis suggests the MTHFR A1298C polymorphism may be a potential risk factor for male infertility, especially in the Asian population.

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“…Methionine synthase is important for maintaining methionine level and preventing homocysteine accumulation. Increased blood homocysteine level have been associated with increased risk of developing cardiovascular disease, infertility, late pregnancy complications such as pre-eclampsia, abruption placenta, intrauterine growth retardation, preterm birth & intrauterine fetal death, birth defects, neural tube defects, Down syndrome, and development of some types of cancer (Eskes 2000;Nelen 2001;Carmel and Jacobsen 2002;Hague 2003;Steegers-Theunissen et al 2004;Tamura and Picciano 2006;Farcas et al 2009;Li et al 2015).…”

Section: Introductionmentioning

confidence: 99%

Predicting the functional and structural consequences of nsSNPs in human methionine synthase gene using computational tools

Desai¹,

Chauhan²

2019

Systems Biology in Reproductive Medicine

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Methionine synthase encoded by the MTR gene is one of the key enzymes involved in the SAM (S-Adenosyl Methionine) cycle catalyzing the conversion of homocysteine to methionine. Methionine plays an important role in the DNA, RNA, protein, phospholipids, and neurotransmitters methylation. It also maintains serum homocysteine level and indirectly regulates de novo nucleotide synthesis and repair. The current study predicted the functional consequences of nsSNPs in human MTR gene using SIFT, PolyPhen2, PROVEAN, SNAP2, PMut, nsSNPAnalyzer, PhD-SNP, SNPs&GO, I-Mutant, MuPro, and iPTREE-STAB. The PTM sites within the protein were predicted using ModPred and the phylogenetic conservations of amino acids & conserved domains of protein were predicted using ConSurf and NCBI conserved domain search tool respectively. The protein 3D structure was generated using SPARKS-X and analyzed using RAMPAGE. Structural deviation was analyzed using TM-Score. STRING analysis was preformed to predict protein-protein interactions. D621G, G682D, V744L, V766E, and R1027W were predicted to be the most deleterious nsSNPs in MTR. R1027 was predicted to having the three PTM sites and G682 & V744 were predicted as highly conserved residues. D621G, G682D, V744L, V776E, and R1027W were predicted to be within conserved domains of methionine synthase. The G682D, V744L, V776E, and R1027W were predicted to alter protein 3D structure. STRING predicted that methionine synthase interacting with 10 different proteins. The present study predicted D621G, G682D, V744L, V766E, and R1027W as functionally and structurally significant nsSNPs in human MTR gene. The present study can provide the significant information for further experimental analysis.

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Association between methionine synthase reductase A66G polymorphism and primary infertility in Chinese males

Cited by 12 publications

References 36 publications

The relevance of MTHFR C677T, A1298C, and MTRR A66G polymorphisms with response to male infertility in Asians

The relevance of MTHFR C677T, A1298C, and MTRR A66G polymorphisms with response to male infertility in Asians

Association between MTHFR A1298C polymorphism and male infertility: A meta-analysis

Predicting the functional and structural consequences of nsSNPs in human methionine synthase gene using computational tools

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