Association between factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations and events of the arterial circulatory system: a meta-analysis of published studies.
BACKGROUND: The association between the inherited gene mutations of factor V, prothrombin, and homocysteine metabolism and venous thromboembolic events is accepted widely; however, their influence on the arterial circulatory system remains controversial. METHODS: We performed a MEDLINE search to identify published case-control and cohort studies correlating the factor V Leiden, prothrombin (PT) G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T (TT genotype) mutations with myocardial infarction, ischemic stroke, or peripheral vascular disease. Studies were included only when they adhered to specific diagnostic criteria for ischemic events and met the published methodological criteria. Odds ratios (ORs) with accompanying 95% CIs were calculated for each mutation and clinical end points with a random-effects model (DerSimonian and Laird method). RESULTS: The association between inherited gene mutations and arterial ischemic events was modest: factor V Leiden mutation (OR, 1.21; 95% CI, 0.99-1.49), PT G20210A mutation (OR, 1.32; 95% CI, 1.03-1.69), and MTHFR TT mutation (OR, 1.20; 95% CI, 1.02-1.41). Subgroup analyses of younger patients (<55 years old) and of women revealed slightly stronger associations overall. CONCLUSIONS: Genetic abnormalities specific to factor V, prothrombin,and homocysteine metabolism increase the risk for myocardial infarction and ischemic stroke, particularly among younger patients and women. Because the overall association is only modest, screening studies should be limited to carefully selected patient populations. The individual propensity for arterial and venous thrombosis is likely influenced by differing local mechanisms, systemic mechanisms, or both.
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