The Factor XII -4C>T Variant and Risk of Common Thrombotic Disorders: A HuGE Review and Meta-Analysis of Evidence From Observational Studies

Coagulation factor XII is involved in thrombus formation and therefore may play a role in the etiology of thrombotic disorders. A common variant in the factor XII (F12) gene (-4C > T, rs1801020) results in decreased plasma levels of this coagulation factor. The existence of associations between low factor XII levels or F12 variants and thrombotic outcomes has been debated for more than a decade. The authors conducted a review and meta-analysis to evaluate the evidence for an association between F12 -4C > T and 2 common thrombotic outcomes: venous thromboembolism and myocardial infarction, which are hypothesized to share some etiologic pathways. MEDLINE, EMBASE, and HuGE Navigator were searched through July 2009 to identify relevant epidemiologic studies, and data were summarized using random-effects meta-analysis. Sixteen candidate gene studies (4,386 cases, 40,089 controls) were analyzed. None of the investigated contrasts reached statistical significance at P < 0.05, apart from a very weak association with myocardial infarction for the TT + CT versus CC contrast (odds ratio = 1.13, 95% confidence interval: 1.00, 1.27). Overall, based on the synthesis of observational studies, the evidence for an association between F12 -4C > T and venous thromboembolism and myocardial infarction is weak.