Correlation of polymorphisms to coagulation and biochemical risk factors for cardiovascular diseases.

Currently, the established risk factors for cardiovascular disease (CVD) are largely environmental in nature. Conflicting studies have suggested that mutations in specific coagulation genes may also provide a genetic basis for CVD risk. We reviewed clinical studies that examined the role of single nucleotide polymorphisms in coagulation and platelet factors, and a biochemical factor to determine if specific genotypes are correlated with patients with a history of arterial thrombotic diseases (acute coronary syndromes or stroke). A meta-analysis was performed on studies for factors II (G20210A variant), V Leiden (G1691A), VII (R353Q), glycoprotein (GP) IIIa receptor (PI(A1/A2)), and methylenetetrahydrofolate reductase (MTHFR, C677T). There was no correlation for factor II or factor V polymorphisms to coronary artery disease (CAD) in 5,607 and 5,431 patients studied, respectively. There was also no correlation for factor II variants and stroke in 3,451 patients studied. For factor V, statistical significance was achieved for the G1691A variant on 3,399 patients with stroke (odds ratio [OR] 1.43, 95% confidence intervals [CI] 1.03 to 1.97). The GP IIIa PI(A1/A2) genotype was associated with increased risk for CAD in 7,920 patients (OR 1.12, 95% CI 1.01 to 1.24), but not for 1,855 patients who had a stroke (OR 0.80, 95% CI 0.62 to 1.04). The combined RQ and RR genotypes of factor VII R353Q were correlated to a reduced risk for CVD in 2,574 patients (OR 0.78, 95% CI 0.65 to 0.93), whereas the QQ genotype had offered more protection (OR 0.53, 95% CI 0.27 to 1.03). The TT homozygous variant of MTHFR was associated with CAD risk in 5,644 patients studied (OR 1.30, 95% CI 1.11 to 1.52) but not for 3,075 patients with stroke. This study shows that for some genes, further studies are unnecessary, whereas for others, no more enrollments are needed. The impact of certain genotypes must be examined in relation to other established risk factors and potentially new therapeutic strategies.