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A systematic overview and meta‐analysis of genetic variation within the folate metabolic network and cardiovascular disease (CVD) risk
Author(s) -
Wernimont Susan M.,
Stover Patrick J.,
Wells Martin T.,
Cassano Patricia A.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.724.15
Subject(s) - mtrr , cystathionine beta synthase , meta analysis , disease , confounding , medicine , bioinformatics , methylenetetrahydrofolate reductase , genetics , gene , biology , genotype , oncology , methionine , amino acid
Dysfunctional folate metabolism has been implicated in chronic diseases including CVD. The relation of the methylene‐tetrahydrofolate reductase enzyme to CVD risk is the subject of several meta‐analyses, yet much less is known about variation in other folate network genes in relation to CVD. Thus, a systematic overview and meta‐analysis of genetic variation in the folate network in relation to CVD was conducted. Fifty‐two genes in the folate network were identified, representing key reactions and linked steps. Four genes had an evidence base sufficient to summarize: cystathionine‐beta‐synthase (CBS, 25 studies), methionine synthase (MTR, 16 studies), methionine synthase reductase (MTRR, 9 studies) and transcobalamin II (TCN2, 4 studies). In CBS, 844ins68 had a differential effect by CVD subtype: for heart disease the variant decreased risk (OR 0.77; 95% CI 0.6, 1.0; I 2 24.2%), for stroke & other vascular disease it increased risk (OR 1.30; 95% CI 1.0, 1.7; I 2 0%). In MTRR, rs1801394 increased the risk of CVD (OR 1.27; 95% CI 0.9, 1.7; I 2 19.3%), and the number of publications precluded subtype analysis. For CBS rs5742905, MTR rs1805087, and TCN2 rs1801198, little or no association with CVD was observed. Thus, the association of genetic variation in the folate network with CVD differs by gene and outcome, and few variants have been studied sufficiently to allow meta‐analysis. Funding: NIH T32 DK007158 ‐33 (SMW). Grant Funding Source NIH T32 DK007158 ‐33 (SMW)