The methylenetetrahydrofolate reductase C677T genotype and the risk of obesity in three large population-based cohorts.

ObjectiveEpidemiological studies have shown that low folate levels are associated with a high body mass index (BMI). These findings have potentially important health implications and warrant further investigation to determine whether a causal relationship exists and the direction of this relationship. The methylenetetrahydrofolate reductase (MTHFR)C677T TTgenotype is associated with reduced folate availability and may be a surrogate for measuring folate levels. We sought to determine whetherMTHFR C677Tgenotype was associated with obesity.DesignWe carried out our study on four populations from three longitudinal studies based in the UK and Denmark in which DNA for genotyping was obtained along with measures of obesity.MethodsOur subjects were taken from the British Women's Heart and Health Study (BWHHS), the Avon Longitudinal Study of Parents and Children (two populations: mothers and children) and the Copenhagen City Heart Study. We performed analyses separately by population, and then carried out a meta-analysis, combining similar populations.ResultsInitial findings in the BWHHS suggested that theTTgenotype may be associated with an increased risk of obesity BMI≥30, however, no association was found with BMI or central adiposity in this cohort. This genotype was not associated with obesity in our other cohorts.ConclusionsOur results suggest that the initial positive finding with obesity in the BWHHS was a chance finding. Our findings do not support a causal effect of low folate on obesity.

Download Full-text

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

Frontiers in Genetics ◽

10.3389/fgene.2021.698590 ◽

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.

Download Full-text

High Body Mass Index and Central Adiposity Is Associated with Increased Risk of Acute Pancreatitis: A Meta-Analysis

Digestive Diseases and Sciences ◽

10.1007/s10620-020-06275-6 ◽

2020 ◽

Author(s):

Dagfinn Aune ◽

Yahya Mahamat-Saleh ◽

Teresa Norat ◽

Elio Riboli

Keyword(s):

Body Mass Index ◽

Acute Pancreatitis ◽

Body Mass ◽

Meta Analysis ◽

High Body Mass Index ◽

Central Adiposity ◽

High Body ◽

Increased Risk

Download Full-text

The association of MTHFR C677T variant with increased risk of ischemic stroke in the elderly population: a meta-analysis of observational studies

BMC Geriatrics ◽

10.1186/s12877-019-1304-y ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Guilin Chang ◽

Zheng Kuai ◽

Jia Wang ◽

Jiayu Wu ◽

Kan Xu ◽

...

Keyword(s):

Ischemic Stroke ◽

Elderly Population ◽

Methylenetetrahydrofolate Reductase ◽

Meta Analysis ◽

Mthfr C677t ◽

The Elderly ◽

Cochrane Library ◽

Case Control Studies ◽

Eligibility Criteria ◽

Increased Risk

Abstract Background C677T point mutation in methylenetetrahydrofolate reductase (MTHFR) gene have been found to be associated with ischemic stroke in general population, while the results seem inconsistent. We aim to assess the association between variant MTHFR C677T variant and increased risk of ischemic stroke and focus on the elderly population. Methods We searched PubMed, Embase, Cochrane Library, and Web of Science for eligible studies. Odds ratios (ORs) were calculated with the two-tailed 95% confidence intervals (CIs) by using a random effects model to evaluate any possible association. Among the Chinese and non-Chinese populations, we conducted a subgroup analysis. Results The electronic database search yielded 1,358 citations as of December 2017; finally, nine case-control studies involving 3,337 subjects fulfilled our eligibility criteria for inclusion in the study. The pooled results showed that MTHFR C677T variant increased the risk of ischemic stroke (OR = 1.23, 95%CI 1.06–1.43, P = 0.0067 for CT + TT vs. CC; OR = 1.18, 95%CI 1.01–1.38, P = 0.0333 for CT vs. CC; OR = 1.41, 95%CI 1.14–1.75, P = 0.0016 for TT vs. CC; OR = 1.27, 95%CI 1.05–1.54, P = 0.0145 for TT vs. CC + CT; OR = 1.18, 95%CI 1.06–1.31, P = 0.0023 for T-allele vs. C-allele). Further subgroup analyses in the Chinese population indicated that MTHFR C677T variant was associated with a higher risk of ischemic stroke. Conclusion Our findings showed that T-allele increases risk for stroke in the pooled sample. This association was statistically significant in the Chinese cohorts and showed a similar trend in the non-Chinese cohorts. (Word count: 237).

Download Full-text

Causal effect of renal function on venous thromboembolism: a two-sample Mendelian randomization investigation

Journal of Thrombosis and Thrombolysis ◽

10.1007/s11239-021-02494-4 ◽

2021 ◽

Author(s):

Shuai Yuan ◽

Maria Bruzelius ◽

Susanna C. Larsson

Keyword(s):

Renal Function ◽

Venous Thromboembolism ◽

Mendelian Randomization ◽

Causal Effect ◽

Meta Analysis ◽

Genome Wide Association Studies ◽

Uk Biobank ◽

Genome Wide ◽

Increased Risk ◽

Mr Study

AbstractWhether renal function is causally associated with venous thromboembolism (VTE) is not yet fully elucidated. We conducted a two-sample Mendelian randomization (MR) study to determine the causal effect of renal function, measured as estimated glomerular filtration rate (eGFR), on VTE. Single-nucleotide polymorphisms associated with eGFR were selected as instrumental variables at the genome-wide significance level (p < 5 × 10−8) from a meta-analysis of 122 genome-wide association studies including up to 1,046,070 individuals. Summary-level data for VTE were obtained from the FinnGen consortium (6913 VTE cases and 169,986 non-cases) and UK Biobank study (4620 VTE cases and 356,574 non-cases). MR estimates were calculated using the random-effects inverse-variance weighted method and combined using fixed-effects meta-analysis. Genetically predicted decreased eGFR was significantly associated with an increased risk of VTE in both FinnGen and UK Biobank. For one-unit decrease in log-transformed eGFR, the odds ratios of VTE were 2.93 (95% confidence interval (CI) 1.25, 6.84) and 4.46 (95% CI 1.59, 12.5) when using data from FinnGen and UK Biobank, respectively. The combined odds ratio was 3.47 (95% CI 1.80, 6.68). Results were consistent in all sensitivity analyses and no horizontal pleiotropy was detected. This MR-study supported a casual role of impaired renal function in VTE.

Download Full-text

Association Between Nonsyndromic Cleft Lip and Palate and 2 Polymorphic Loci: A Meta-Analysis

The Cleft Palate-Craniofacial Journal ◽

10.1177/1055665620962686 ◽

2020 ◽

pp. 105566562096268

Author(s):

Yusi Wang ◽

Xueyuan Jia ◽

Yuandong Qiao ◽

Lidan Xu ◽

Xuelong Zhang ◽

...

Keyword(s):

Odds Ratio ◽

Cleft Lip ◽

Methylenetetrahydrofolate Reductase ◽

Cleft Lip And Palate ◽

Meta Analysis ◽

Craniofacial Development ◽

Asian Group ◽

Potential Association ◽

Increased Risk ◽

The Relationship

Objectives: The relationship between Noggin ( NOG) and methylenetetrahydrofolate reductase and nonsyndromic cleft lip and palate (NSCLP) has been reported participate in craniofacial development but need further evidence. To indicate the susceptibility between the 2 genes and NSCLP, rs227731 and rs1801131 polymorphisms were included in the present research. This research may provide some genetic clues for disease detection and surveillance. Design: Seventeen studies including 4023 cases and 5691 controls were provided for meta-analysis, and odds ratio (OR) with 95% CI were obtained to estimate NSCLP risk. Results: Our analysis suggested potential association of rs227731C on increasing the risk of NSCLP in the Caucasian group and total group but not Asian group under all models: allele (OR = 1.45, 95% CI = 1.21-1.75, P < .0001), homozygote (OR = 2.03, 95% CI = 1.42-2.90, P < .0001), heterozygote (OR = 1.44, 95% CI = 1.19-1.73, P = .0001), dominant (OR = 1.61, 95% CI = 1.27-2.04, P < .0001), and recessive models (OR = 1.63, 95% CI = 1.25-2.12, P = .0003). Besides, increased risk is related to rs1801131 in Asian group under 3 models: allele (OR = 1.24, 95% CI = 1.06-1.44, P = .006), heterozygote (OR = 1.24, 95% CI = 1.02-1.52, P = .03), and dominant models (OR = 1.29, 95% CI = 1.06-1.56, P = .009). Conclusions: Our analysis indicates polymorphisms rs227731 and rs1801131 are associated with NSCLP, with predominance of different ethnic group and deepen understanding of NSCLP.

Download Full-text

The correlation between methylenetetrahydrofolate reductase gene 677C > T polymorphism and fetal congenital defects: A meta-analysis

Pteridines ◽

10.1515/pteridines-2020-0002 ◽

2020 ◽

Vol 31 (1) ◽

pp. 9-17

Author(s):

Dexia Li ◽

Enxia Wang ◽

Xia Gao ◽

Ping Li

Keyword(s):

Single Nucleotide Polymorphism ◽

Publication Bias ◽

Methylenetetrahydrofolate Reductase ◽

Meta Analysis ◽

Random Effect ◽

Congenital Defects ◽

Nucleotide Polymorphism ◽

Case Control Studies ◽

Single Nucleotide ◽

Increased Risk

AbstractObjective To investigate the correlation between the methylenetetrahydrofolate reductase (MTHFR) gene 677C> T polymorphism and fetal congenital defects.Method Original studies relevant to the MTHFR gene 677C>T single nucleotide polymorphism and fetal congenital defects were systematically searched in the electronic databases of Medline, EMBSE and China National Knowledge Infrastructure (CNKI). All relevant publications were screened for inclusion in the present work. The correlation between the MTHFR gene 677C > T single nucleotide polymorphism and the occurrence of fetal congenital defects was expressed as an odds ratio (OR) and its 95% confidence interval (95% CI). Publication bias was assessed by Begg’s funnel plot and Egger’s line regression test.Results Nineteen case-control studies were ultimately included in the present meta-analysis. The pooled results indicated that the general risk of fetal congenital defects was significantly elevated in subjects with the 677T allele of the MTHFR gene in dominant (OR=1.07,95%CI:1.03-1.12, P<0.05), homozygous (OR=1.17,95%CI:1.06-1.30, P<0.05) and recessive genetic models (OR=1.16,95%CI:1.03-1.31, P<0.05) through the random effect method. However, significant publication bias was identified upon pooling the individual data and evaluating the correlation.Conclusion According to the present evidence, the MTHFR gene 677C>T single nucleotide polymorphism is correlated with poor pregnancy outcomes, and subjects with the T allele have an increased risk of developing general fetal congenital defects.

Download Full-text

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

Clinical Rheumatology ◽

10.1007/s10067-016-3348-0 ◽

2016 ◽

Vol 36 (2) ◽

pp. 287-297 ◽

Cited By ~ 10

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

Download Full-text

Factor V Leiden Is Associated with Premature Myocardial Infarction.

Blood ◽

10.1182/blood.v112.11.1817.1817 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1817-1817

Author(s):

Flora Peyvandi ◽

Marta Spreafico ◽

Luisa Foco ◽

Luisa Bernardinelli ◽

Stefano Duga ◽

...

Keyword(s):

Risk Factors ◽

Myocardial Infarction ◽

Meta Analysis ◽

Large Population ◽

Factor V Leiden ◽

Coagulation Factor ◽

Factor V ◽

Gain Of Function ◽

Increased Risk ◽

Meta Analyses

Abstract Plasma levels of haemostatic proteins involved in coagulation and fibrinolysis may represent an important intermediate phenotype for cardiovascular diseases (because increased levels of these proteins have been associated with an increased/reduced risk of thrombosis). However, investigation in arterial diseases of gain-of-function polymorphisms of genes encoding coagulation factor V (F5 G1691A) and prothrombin (F2 G20210A), established risk factors for venous thrombosis, have generally indicated weak or no associations in a number of conflicting and inconclusive reports [Ye et al., Lancet2006;367:651–8]. These negative results might be due to the sample size, too small to reliably assess relatively small genetic effects. Recently, a meta-analysis of 4,944 patients and 7,090 controls on the association of the F2 G20210A and ischemic heart disease [Burzotta et al, Heart2004;90:82–6], and a meta-analysis of 66,155 cases and 91,307 controls on the association of haemostatic genetic variants and coronary artery disease (CAD) [Ye et al, Lancet2006;367:651–8], found that either F2 G20210A and F5 G1691A polymorphisms were associated with a moderately increased risk of CAD. Results from these meta-analyses, large but based respectively upon 19 and 100 different studies all of rather small size, should be taken cautiously. Considering that genetic factors play a particularly important role in CAD occurring in the young, with usually less coronary atherosclerosis and a high prevalence of normal or near-normal coronary angiograms, we chose to replicate the meta-analysis results by investigating an adequately large population of 1,864 Italian patients who developed myocardial infarction (MI) before the age of 45 yrs (1,655 men and 209 women) and 1,864 age- and sex-matched controls. Genotyping was performed by Sequenom MassARRAY platform. Statistical analysis was performed fitting a conditional logistic model with STATA 9.2 software. Our results showed that the minor A allele of F5 G1691A (2.6% frequency in cases and 1.7% in controls) was associated with a moderately increased risk of MI (OR:1.59; 95% CI:1.14–2.20; P=0.006). The association remained statistically significant after adjustment for traditional risk factors, including diabetes, smoking, hypertension, and hypercholesterolemia (OR:1.81; 95% CI:1.14–2.87; P=0.012). The minor A allele of F2 G20210A (2.4% frequency in cases and 1.9% in controls) was not associated with the risk of MI (OR:1.27; 95% CI:0.93–1.74; P=0.133), even after adjustment (OR:1.19; 95% CI:0.77–1.85; P=0.429). In conclusion, results of the previous meta-analyses are replicated only partially in this cohort of young MI patients, the largest investigated so far, as only the gain-of-function variant F5 G1691A (but not F2 G20210A) was associated with an increased risk of MI. Our results suggest that anticoagulant drugs might be considered for secondary prophylaxis of MI in patients with the F5 gene variant, who carry a procoagulant phenotype.

Download Full-text