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.