Abstract 4882: Factor V Leiden, But Not Prothrombin G20120A, Is Associated With Premature Myocardial Infarction
Background. Gain-of-function polymorphisms of genes encoding coagulation factor V (F5 G1691A) and prothrombin (F2 G20210A) increase circulating thrombin and are established risk factors for venous thrombosis. In atherothrombotic diseases, several studies yielded inconclusive results, mainly because sample sizes were too small owing to the low frequency of variant alleles. A meta-analysis of 66,155 cases and 91,307 controls (Lancet 2006;367:651) found that either polymorphism was associated with a moderately increased risk of coronary artery disease (CAD). Results from this meta-analysis, large but based upon 100 different studies all of rather small size, should be taken cautiously. Considering that genetic factors play a particularly important role in CAD occurring in the young, we chose to replicate the meta-analysis results by investigating an adequately large population of Italian patients who had developed myocardial infarction (MI) before the age of 45 yrs.
Matherials and methods. Genotyping was performed by Sequenom MassARRAY platform. Statistical analysis was performed fitting a conditional logistic model with STATA 9.2 software.
Results. In 1864 patients with MI (1655 men and 209 women) and 1864 age- and sex-matched controls, the minor A allele of F5 G1691A (2.6% frequency in cases and 1.7% in controls) was associated with a moderately increased risk of MI (OR:1.59;95% CI:1.14 –2.20; P=0.006). The association remained statistically significant after adjustment for traditional risk factors, including diabetes, smoking, hypertension and hypercholesterolemia (OR:1.81;95% CI:1.14 –2.87; P=0.012). The minor A allele of F2 G20210A, (2.4% frequency in cases and 1.9% in controls) was not associated with the risk of MI (OR:1.27;95% CI:0.93–1.74; P=0.133), even after adjustment (OR:1.19;95% CI:0.77–1.85; P=0.429).
Conclusions. In this cohort of young MI patients, the largest investigated so far, the gain-of-function variant F5 G1691A (but not F2 G20210A) was associated with an increased risk of MI. Results of the previous meta-analysis are replicated only partially. Our results suggest that patients with of the FV gene variant, who carry a procoagulant phenotype, anticoagulant drugs might be considered for secondary prophylaxis of MI.