Factor XIII val34leu and the risk of myocardial infarction.

BACKGROUND AND OBJECTIVE Recent studies have suggested an association between a genetic variation in the coagulation factor XIII (FXIII Val34Leu) and decreased risk of vascular thrombosis. DESIGN AND METHODS We investigated the frequency of the FXIII Val34Leu polymorphism in 150 consecutive, unrelated and relatively young (<55 years) survivors of myocardial infarction (MI) with angiographically-proven severe coronary atherosclerosis and in 150 age-, gender- and race-matched controls. RESULTS FXIII Val34Leu was detected in 54/150 patients and 73/150 controls, yielding an overall odds ratio (OR) for MI of 0.6 (CI95: 0.4-0.9). Homozygosity for FXIII Val34Leu was found in 4/150 patients and in 12/150 controls, yielding an OR for MI of 0.26 (CI95: 0.08-0.9). The OR for heterozygotes was 0.65 (CI95: 0.4-1.1). FXIII Val34Leu carriership decreased the risk of MI related to metabolic risk factors (RF) (hypertension, diabetes, dyslipidemia, and obesity): non-carriers in the presence of a metabolic RF had a 13.9-fold higher risk of MI, whereas in carriers with a metabolic RF the risk was reduced to 6.8. FXIII Val34Leu also attenuated the risk of MI among smokers. Non-carrier smokers had a 6.1-fold higher risk (CI95: 3.1-11.9), whereas the risk among smokers carrying FXIII Val34Leu was 3.9 (CI95: 1.9-8.1). INTERPRETATION AND CONCLUSIONS FXIII Val34Leu confers a significant protective effect against the occurrence of MI in relatively young patients. FXIII Val34Leu exhibits a gene dosage effect: the protective effect was particularly strong in homozygous carriers, and heterozygosity conferred moderate protection. Finally, FXIII Val34Leu seems to reduce the risk of MI related to major cardiovascular risk factors.