Associations of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms with genetic susceptibility to rheumatoid arthritis: a meta-analysis

2016 ◽  
Vol 36 (2) ◽  
pp. 287-297 ◽  
Author(s):  
Han Cen ◽  
Hua Huang ◽  
Li-Na Zhang ◽  
Li-Ya Liu ◽  
Li Zhou ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Genetic Susceptibility ◽  
Methylenetetrahydrofolate Reductase ◽  
Meta Analysis ◽  
Mthfr C677t

scholarly journals Association Between MTHFR Polymorphisms and the Risk of Essential Hypertension: An Updated Meta-analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Hao Meng ◽  
Shaoyan Huang ◽  
Yali Yang ◽  
Xiaofeng He ◽  
Liping Fei ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Essential Hypertension ◽  
Methylenetetrahydrofolate Reductase ◽  
Meta Analysis ◽  
Mthfr C677t ◽  
Cochrane Library ◽  
Mthfr Polymorphisms ◽  
Southeast Asians ◽  
Increased Risk ◽  
Meta Analyses

Background: Since the 1990s, there have been a lot of research on single-nucleotide polymorphism (SNP) and different diseases, including many studies on 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphism and essential hypertension (EH). Nevertheless, their conclusions were controversial. So far, six previous meta-analyses discussed the internal relationship between the MTHFR polymorphism and EH, respectively. However, they did not evaluate the credibility of the positive associations. To build on previous meta-analyses, we updated the literature by including previously included papers as well as nine new articles, improved the inclusion criteria by also considering the quality of the papers, and applied new statistical techniques to assess the observed associations. Objectives: This study aims to explore the degree of risk correlation between two MTHFR polymorphisms and EH. Methods: PubMed, EMBASE, the Cochrane Library, CNKI, and Wan Fang electronic databases were searched to identify relevant studies. We evaluated the relation between the MTHFR C677T (rs1801133) and A1298C (rs1801131) polymorphisms and EH by calculating the odds ratios (OR) as well as 95% confidence intervals (CI). Here we used subgroup analysis, sensitivity analysis, cumulative meta-analysis, assessment of publication bias, meta-regression meta, False-positive report probability (FPRP), Bayesian false discovery probability (BFDP), and Venice criterion. Results: Overall, harboring the variant of MTHFR C677T was associated with an increased risk of EH in the overall populations, East Asians, Southeast Asians, South Asians, Caucasians/Europeans, and Africans. After the sensitivity analysis, positive results were found only in the overall population (TT vs. CC: OR = 1.14, 95% CI: 1.00–1.30, Ph = 0.032, I2 = 39.8%; TT + TC vs. CC: OR = 1.15, 95% CI: 1.01–1.29, Ph = 0.040, I2 = 38.1%; T vs. C: OR = 1.14, 95% CI: 1.04–1.25, Ph = 0.005, I2 = 50.2%) and Asian population (TC vs. CC: OR = 1.14, 95% CI: 1.01–1.28, Ph = 0.265, I2 = 16.8%; TT + TC vs. CC: OR = 1.17, 95% CI: 1.04–1.30, Ph = 0.105, I2 = 32.9%; T vs. C: OR = 1.10, 95% CI: 1.02–1.19, Ph = 0.018, I2 = 48.6%). However, after further statistical assessment by FPRP, BFDP, and Venice criteria, the positive associations reported here could be deemed to be false-positives and present only weak evidence for a causal relationship. In addition, when we performed pooled analysis and sensitivity analysis on MTHFR A1298C; all the results were negative. Conclusion: The positive relationships between MTHFR C677T and A1298C polymorphisms with the susceptibility to present with hypertension were not robust enough to withstand statistical interrogation by FPRP, BFDP, and Venice criteria. Therefore, these SNPs are probably not important in EH etiology.

scholarly journals Assessing the Association between the Methylenetetrahydrofolate Reductase (MTHFR) 677C->T Polymorphism on Blood Folate Concentrations: A Systematic Review and Meta-analysis of Trials and Observational Studies

2015 ◽  
pp. 650-651
Author(s):  
Becky Tsang ◽  
Amy Cordero ◽  
Claire Marchetta ◽  
Joseph Mulinare ◽  
Patricia Mersereau ◽  
...  
Keyword(s):  
Systematic Review ◽  
Protein Binding ◽  
Observational Studies ◽  
Methylenetetrahydrofolate Reductase ◽  
Meta Analysis ◽  
Mthfr C677t ◽  
Review Of Literature ◽  
Binding Assays ◽  
Lower Blood ◽  
Meta Analyses

Objectives: The methylenetetrahydrofolate reductase (MTHFR) 677C->T polymorphism is a risk factor for neural tube birth defects (NTDs). The T allele produces an enzyme with reduced folate processing capacity, which has been shown to produce lower blood folate concentrations in some studies. Our objective was to assess the association between MTHFR C677T genotypes (CC, CT, TT) and blood folate concentrations among women aged 12-49 years. Methods: We conducted a systematic review of literature published between 1/1992-7/2013 to identify controlled trials and observational studies that reported serum, plasma, or red blood cell (RBC) folate concentrations and MTHFR C677T genotype. We applied a Bayesian random-effects model to predict differences in blood folate concentrations between MTHFR C677T genotypes, stratified by folate assay. Results: Thirty-eight studies met criteria for inclusion. Serum/plasma folate concentrations showed a consistent genotype trend with the highest concentrations for CC (CC > CT > TT) regardless of assay type. RBC folate concentrations measured by microbiologic assay also demonstrated this trend; however, this trend was reversed (CC < CT < TT) in studies using protein-binding assays. Conclusions: Meta-analyses results showed blood folate concentrations differed by assay type and genotype. Previous evidence has shown that RBC folate concentrations measured with a radioimmunoassay requires adjustment for genotype-dependent folate recovery; our results suggest that other protein-binding assays could have similar limitations. Compared to CC individuals, TT individuals have lower blood folate concentrations, which may increase a woman's risk for an NTD-affected pregnancy.

scholarly journals Association of MTHFR C677T and A1298C Polymorphisms with Susceptibility to Chronic Lymphocytic Leukemia: A Systematic Review and Meta-Analysis

2021 ◽  
Author(s):  
Atefeh RAOUFI ◽  
Behdad RAHIMI KELARIJANI ◽  
Hamid Reza AHADI ◽  
Bahareh HASSANI DERAKHSHANDEH ◽  
Zahra NOOROOLLAHZADEH ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Methylenetetrahydrofolate Reductase ◽  
Meta Analysis ◽  
Mthfr C677t ◽  
Gene Interaction ◽  
Lymphocytic Leukemia ◽  
Mthfr Polymorphism ◽  
Mthfr Polymorphisms ◽  
Comprehensive Search ◽  
Allelic Model

Background: The relation between methylenetetrahydrofolate reductase)MTHFR( polymorphisms and the risk of developing Chronic lymphocytic leukemia (CLL) is not still clear, while there are reports about the association of MTHFR C677T and A1298C polymorphisms with developing CLL, there are other reports that rolled out the association of MTHFR polymorphisms with developing CLL. Therefore herein we carried out this meta-analysis to clear the association of MTHFR polymorphisms with the risk of CLL Methods: A comprehensive search was performed through PubMed, Scopus and Embase from inception to Aug 2020. Odds ratios (OR) with their corresponding 95% confidence intervals (CI) for five possible genetic models were calculated. Heterogeneity was evaluated using the Cochran Q test and the I2 statistic. Results: Totals of 1290 cases and 1887 controls for the C677T polymorphism and 1117 cases and 1256 controls for the A1298C polymorphism were included in our analysis. Analyzing the MTHFR C677T and A1298C polymorphisms genotypes showed an association between MTHFR polymorphism at A1298C under Allelic model and the risk of CLL (OR = 1.12, 95% CI = 1.01–1.25), however there was no association between MTHFR polymorphism at MTHFR C677T and risk of CLL. Conclusion: The risk of developing CLL might be associated with MTHFR polymorphism at A1298C under allelic model and not associated with MTHFR polymorphisms at C677T, However, further studies considering other factors such as age, gender, ethnicity, gene-gene interaction and environmental condition are needed to clear the true association of MTHFR polymorphisms with CLL.  

scholarly journals Association of Methylenetetrahydrofolate Reductase C677T Gene Polymorphisms with Mild Cognitive Impairment Susceptibility: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Jiahui Sun ◽  
Xuefan Jiang ◽  
Ming Zhao ◽  
Lina Ma ◽  
Hui Pei ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Gene Polymorphisms ◽  
Large Scale ◽  
Methylenetetrahydrofolate Reductase ◽  
Meta Analysis ◽  
Mthfr C677t ◽  
Gene Variants ◽  
China National Knowledge Infrastructure ◽  
Knowledge Infrastructure

Background. Methylenetetrahydrofolate reductase (MTHFR) C677T (rs1801133) gene polymorphisms are related to a growing risk of Alzheimer’s disease; however, whether this association applies to mild cognitive impairment (MCI) remains unclear. Objective. We conducted this meta-analysis to evaluate the contribution of MTHFR C677T (rs1801133) gene variants to the risk of MCI. Methods. PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases were searched from their inception to March 21, 2021, with language restricted to English or Chinese. We used fixed or random effects to examine the association between MTHFR C677T (rs1801133) gene variants and MCI susceptibility. Forest plots of pooled odds ratios (ORs) and 95% confidence intervals (CIs) were generated. Results. Eight articles with 2,175 participants were included in the present meta-analysis. There was no significant association between MTHFR C677T (rs1801133) gene variants and MCI susceptibility under the allelic (OR, 1.318; 95% CI, 0.964–1.801; p = 0.084 ), dominant (OR, 1.296; 95% CI, 0.925–1.817; p = 0.132 ), recessive (OR, 1.397; 95% CI, 0.845–2.312; p = 0.193 ), heterozygous (OR, 1.031; 95% CI, 0.855–1.243; p = 0.749 ), or homozygous (OR, 1.506; 95% CI, 0.850–2.667; p = 0.160 ) models. Conclusion. The results suggest that MTHFR C677T (rs1801133) gene polymorphisms are not associated with MCI susceptibility. However, large-scale studies covering various factors are required.

scholarly journals An evidence-based approach to globally assess the covariate-dependent effect of MTHFR SNP rs1801133 on plasma homocysteine: a systematic review and meta-analysis

2017 ◽  
Author(s):  
Huifeng Jin ◽  
Haojie Cheng ◽  
Wei Chen ◽  
Xiaoming Sheng ◽  
Mark Brown ◽  
...  
Keyword(s):  
Methylenetetrahydrofolate Reductase ◽  
Meta Analysis ◽  
Mthfr C677t ◽  
Evidence Based ◽  
Single Nucleotide ◽  
Dependent Effect ◽  
The Public ◽  
Modifying Effect ◽  
Total Homocysteine ◽  
Plasma Total Homocysteine

BackgroundThe single nucleotide polymorphism (SNP) of the gene Methylenetetrahydrofolate Reductase (MTHFR) C677T (or rs1801133) is the most established genetic factor that increases plasma total homocysteine (tHcy) and consequently results in hyperhomocysteinemia. Yet given the limited penetrance of this genetic variant, it is necessary to individually predict the risk of hyperhomocysteinemia for a rs1801133 carrier.ObjectiveWe hypothesized that variability of this genetic risk is largely due to the presence of factors (covariates) that serve as effect modifiers and/or confounders, such as folic acid (FA) intake, and aimed to assess this risk in the complex context of these covariates.DesignWe systematically extracted from published studies the data of tHcy, rs1801133, and any previously reported rs1801133 covariates. The resulting meta-dataset was first used to analyze the covariates’ modifying effect by meta regression and other statistical means. Subsequently, we stratified tHcy data by the rs1801133 genotypes and analyzed under each genotype the variability of the risk resulted from the covariates’ confounding.ResultsThe dataset contains data of 36 rs1801133 covariates that were collected from 114,448 subjects and 249 qualified studies, among which 6 covariates (sex, age, race, FA intake, smoking, and alcohol consumption) are the most frequently informed and therefore included for statistical analysis. The effect of rs1801133 on tHcy exhibits significant variability that can be attributed to effect modification and, to a larger degree, confounding by these covariates. Via statistical modeling, we predicted the covariate-dependent risk of tHcy elevation and hyperhomocysteinemia in a systematic manner.Conclusionswe demonstrated an evidence-based approach that globally assesses the covariate-dependent effect of rs1801133 on tHcy. The results should assist clinicians in interpreting the rs1801133 data from genetic testing for their patients. Such information is also important for the public that increasingly receives genetic data from commercial services without interpretation of its clinical relevance.

scholarly journals Methylenetetrahydrofolate reductase gene C677T polymorphism and risk of alcohol dependence

2020 ◽  
Author(s):  
Vandana Rai ◽  
Pradeep Kumar
Keyword(s):  
Alcohol Dependence ◽  
Methylenetetrahydrofolate Reductase ◽  
Meta Analysis ◽  
Mthfr C677t ◽  
Mthfr Gene ◽  
Random Effects Model ◽  
C677t Polymorphism ◽  
Mthfr C677t Polymorphism ◽  
Reductase Gene ◽  
Methylenetetrahydrofolate Reductase Gene

AbstractAlcohol dependence is a complex neuropsychiatric disorder. Numerous studies investigated association between MTHFR gene C677T polymorphism and alcohol dependence (AD), but the results of this association remain conflicting. Accordingly, authors conducted a meta-analysis to further investigate such an association. PubMed, Elsevier Science Direct and Springer Link databases were searched for studies on the association between the MTHFR C677T polymorphism and AD. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using the fixed- or random-effects model. Statistical analysis was performed with the software program MetaAnayst and MIX.A total of 11 articles were identified through a search of electronic databases, up to February 28, 2020. The results of the present meta-analysis did not show any association between MTHFR C677T polymorphisms and AD risk (for T vs. C: OR = 1.04, 95% CI = 0.88-1.24; CT vs. CC: OR=1.02, 95%CI= 0.62-1.68; for TT + CT vs. CC: OR = 1.10, 95% CI = 0.94-1.29; for TT vs. CC: OR = 1.01, 95% CI = 0.66-1.51; for TT vs. CT + CC: OR = 0.97, 95% CI = 0.66-1.40). Results of subgroup analysis showed no significant association between MTHFR C677T polymorphism with AD in Asian as well as in Caucasian population. In conclusion, C677T polymorphism is not a risk factor for alcohol dependence.

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