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Review
. 2005 Nov 5;331(7524):1053.
doi: 10.1136/bmj.38611.658947.55. Epub 2005 Oct 10.

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?

Sarah J Lewis  1 , Shah Ebrahim, George Davey Smith
Affiliations
Review

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?

Sarah J Lewis et al. BMJ. .

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.

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Figures

Fig 1
Fig 1
Results of search strategy
Fig 2
Fig 2
Association between MTHFR C677T polymorphism and coronary heart disease (TT versus CC genotype). *Unpublished data taken from Klerk et al, 2002 meta-analysis
See this image and copyright information in PMC

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References

    1. Ford ES, Smith SJ, Stroup DF, Steinberg KK, Mueller PW, Thacker SB. Homocyst(e)ine and cardiovascular disease: a systematic review of the evidence with special emphasis on case-control studies and nested case-control studies. Int J Epidemiol 2002;31: 59-70. - PubMed
    1. Brattstrõm L, Wilcken DEL. Homocysteine and cardiovascular disease: cause or effect? Am J Clin Nutr 2000;72: 315-23. - PubMed
    1. Ueland PM, Refsum H, Beresford SAA, Vollset SE. The controversy over homocysteine and cardiovascular risk. Am J Clin Nutr 2000;72: 324-32. - PubMed
    1. Clarke R. An updated review of the published studies of homocysteine and cardiovascular disease. Int J Epidemiol 2002;31: 70-1. - PubMed
    1. Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ 2002;325: 1202-6. - PMC - PubMed