Background: Variants of certain haemostatic genes(such as that encoding factor V Leiden) are involved in the development of venous thrombosis, but studies of such variants in coronary disease have reported apparently conflicting results. We did meta-analyses on seven such haemostatic genetic variants for which the available evidence on each comprises at least 5000 coronary disease cases and at least 5000 controls. Methods: Meta-analyses were done of 191 studies in relation to factor V G1691A(ie, factor V Leiden), factor VII G10976A, prothrombin G20210A, plasminogen activator inhibitor-1(PAI-1) [-675] 4G/5G, and three platelet glycoprotein(GP)receptor variants(GPIa C807T, GPIbα T[-5]C,GPIIIa C1565T), involving a total of 66 155 coronary disease cases and 91 307 controls. We explored potential sources of heterogeneity. Findings: In a combined analysis of all studies, the per-allele relative risks(RR) for coronary disease of factor V 1691A and of prothrombin 20210A were 1.17(95% CI 1.08-1.28) and 1.31(1.12-1.52), respectively. Combined analyses of studies of the PAI-1 [-675] 4G variant yielded a per-allele relative risk for coronary disease of 1.06(1.02-1.10), but there was an indication of publication bias in these studies. Combined analyses of the factor VII 10976A, GPIa 807T, GPIbα [-5]C, and GPIIIa 1565T variants showed no significant overall associations with coronary disease, yielding per-allele RRs of 0.97(0.91-1.04), 1.02(0.97-1.08), 1.05(0.96-1.13), and 1.03(0.98-1.07) , respectively. Interpretation: The 1691A variant of the factor V gene and the 20210A variant of the prothrombin gene, both of which increase circulating thrombin generation, might each be moderately associated with the risk of coronary disease. Further studies are merited to assess these associations in greater detail(including any gene-gene and gene-environment interactions) and to determine any implications with regard to potential therapies designed to reverse patients prothrombotic phenotype, such as selective plasma factor V or factor Xa inhibition.
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