Dataset Information

Meta-analysis of MTHFR 677C->T polymorphism and coronary heart disease: does totality of evidence support causal role for homocysteine and preventive potential of folate?

ABSTRACT:

Objectives

To investigate the association between the MTHFR 677C-->T polymorphism and coronary heart disease, assessing small study bias and heterogeneity between studies.

Data sources

Medline and Embase citation searches between January 2001 and August 2004; no language restrictions.

Study selection

Case-control and prospective studies of association between MTHFR 677C-->T variant and myocardial infarction, coronary artery occlusion, or both; 80 studies were included.

Data extraction

Data on genotype frequency and mean homocysteine concentrations by genotype were extracted. Odds ratios were calculated for TT genotype versus CC genotype. Heterogeneity was explored, with stratification by geographical region of the study samples, and meta-regression by difference in mean serum homocysteine concentrations (CC minus TT genotypes) was carried out.

Results

26,000 cases and 31,183 controls were included. An overall random effects odds ratio of 1.14 (95% confidence intervals 1.05 to 1.24) was found for TT versus CC genotype. There was strong evidence of heterogeneity (P < 0.001, I2 = 38.4%), which largely disappeared after stratification by geographical region. Odds ratios in Europe, Australia, and North America attenuated towards the null, unlike those in the Middle East and Asia.

Conclusions

No strong evidence exists to support an association of the MTHFR 677 C-->T polymorphism and coronary heart disease in Europe, North America, or Australia. Geographical variability may be due to higher folate intake in North America and Europe or to publication bias. The conclusion drawn from previous meta-analyses that folic acid, through lowering homocysteine, has a role in prevention of cardiovascular disease is in some doubt.

SUBMITTER: Lewis SJ

PROVIDER: S-EPMC1283183 | biostudies-literature | 2005 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Meta-analysis of MTHFR 677C->T polymorphism and coronary heart disease: does totality of evidence support causal role for homocysteine and preventive potential of folate?

Lewis Sarah J SJ Ebrahim Shah S Davey Smith George G

BMJ (Clinical research ed.) 20051010 7524

<h4>Objectives</h4>To investigate the association between the MTHFR 677C-->T polymorphism and coronary heart disease, assessing small study bias and heterogeneity between studies.<h4>Data sources</h4>Medline and Embase citation searches between January 2001 and August 2004; no language restrictions.<h4>Study selection</h4>Case-control and prospective studies of association between MTHFR 677C-->T variant and myocardial infarction, coronary artery occlusion, or both; 80 studies were included.<h4>D ...[more]

PMID: 16216822

Similar Datasets

Project description:Importance:Strong evidence links high total serum homocysteine (tHcy) and low methionine (Met) levels with higher risk of ischemic disease, but other cardiovascular (CV) diseases may also be associated with their pleiotropic effects. Objectives:To investigate the association of serum concentrations of tHcy and Met with the rate of CV multimorbidity development in older adults and to explore the role of methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism in this association. Design, Setting, and Participants:The Swedish National Study on Aging and Care in Kungsholmen is a cohort study of randomly selected individuals aged 60 years or older. The present study included data on 1969 individuals with complete information and without CV diseases at baseline, collected from the baseline examination (2001-2004) to the fourth follow-up (2013-2016). Data analysis was conducted from January to May 2019. Exposures:Concentrations of tHcy and Met were measured from nonfasting venous blood samples. The Met:tHcy ratio was considered a possible indicator of methylation activity. MTHFR status was dichotomized as any T carriers vs noncarriers. Main Outcome and Measures:The number of CV diseases at each wave was ascertained based on medical interviews and records, laboratory test results, and drug data. Linear mixed models were used to study the association of baseline tHcy and Met levels and the rate of CV multimorbidity development, adjusting for sociodemographic characteristics, CV risk factors, chronic disease burden, and drug use. Results:Of 1969 participants, most were women (1261 [64.0%]), with a mean (SD) age of 70.9 (9.8) years; 1703 participants (86.6%) had at least a high school level of education. Baseline measurements of serum tHcy, Met, and the Met:tHcy ratio were associated with the rate of CV disease accumulation (tHcy: β = 0.023 per year; 95% CI, 0.015 to 0.030; P < .001; Met: β = -0.007 per year; 95% CI, -0.013 to -0.001; P = .02; Met:tHcy ratio: β = -0.017 per year; 95% CI, -0.023 to -0.011; P < .001). The association between low Met concentrations and the rate of CV multimorbidity development was restricted to the group with CT/TT alleles of MTHFR (β = 0.023 per year; 95% CI, 0.006 to 0.041; P = .009). Results remained largely significant when individual CV diseases were removed from the total count 1 at a time (eg, ischemic heart disease, tHcy: β = 0.023 per year; 95% CI, 0.013 to 0.027; P < .001; Met: β = -0.006 per year; 95% CI, -0.011 to -0.0003; P = .04; Met:tHcy ratio: β = -0.015 per year; 95% CI, -0.020 to -0.009; P < .001). Conclusions and Relevance:In this study, high tHcy and low Met levels were associated with faster CV multimorbidity development in older age. The interactive association of Met concentrations and MTHFR polymorphism, together with the association found for the Met:tHcy ratio, point toward the relevance of impaired methylation in the pathogenesis of CV aging.

Dataset Information

Meta-analysis of MTHFR 677C->T polymorphism and coronary heart disease: does totality of evidence support causal role for homocysteine and preventive potential of folate?

Objectives

Data sources

Study selection

Data extraction

Results

Conclusions

Publications

Meta-analysis of MTHFR 677C->T polymorphism and coronary heart disease: does totality of evidence support causal role for homocysteine and preventive potential of folate?

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets