G20210A prothrombin gene polymorphism and prothrombin activity in subjectswith or without angiographically documented coronary artery disease

Background-G20210A prothrombin mutation has been associated with high proth rombin levels and an increased risk of venous thrombosis. The role of this common polymorphism, as well as that of prothrombin levels, in determining the risk of arterial disease is still somewhat controversial. Methods and Results-We determined the prevalence of the G20210A mutation an d prothrombin activity in 660 individuals, of whom 436 had angiographically documented severe coronary artery disease (CAD patients) and 224 had norma l coronary angiography (CAD-free control subjects). Heterozygosity for the 20210A allele was found in 5.3% of the CAD patients versus 3.1% of the CAD- free subjects (P=0.21). Similarly, no statistically significant difference was found between CAD patients with or without previous myocardial infarcti on (4.5% versus 5.3%, respectively; P=0.73). The genotype-phenotype correla tion study showed a significant influence of the 20210A allele on prothromb in activity, with higher levels in carriers compared with noncarriers (153. 2% versus 122.2%, respectively; P<0.001). Prothrombin activity was signific antly higher in CAD patients than in CAD-free subjects (132.8% versus 123.3 %, respectively; P<0.005), By multiple logistic regression, prothrombin act ivity in the upper tertile of the control distribution was significantly as sociated with CAD compared with prothrombin activity in the lower tertile ( adjusted odds ratio 1.86, 95% CI 1.01 to 3.4). Conclusions-In a population with a clear-cut definition of the phenotype, t he G20210A prothrombin mutation was not significantly associated, per se, w ith either angiographically documented CAD or myocardial infarction, wherea s it significantly influenced prothrombin activity. In our population, high prothrombin activity itself was independently associated with CAD but not with the presence or absence of previous myocardial infarction.