ASSOCIATION OF A COMMON POLYMORPHISM IN THE FACTOR-XIII GENE WITH MYOCARDIAL-INFARCTION

Factor XIII when activated by thrombin, crosslinks fibrin, however its role in thrombotic disorders is unknown. A common point mutation (G-- >T) in exon 2 of the A-subunit gene which codes for an amino acid chan ge three amino acids from the thrombin activation site (Factor XIIIVa1 34Leu) is a candidate for a role in the pathogenesis of acute myocardi al infarction. Factor XIII genotype frequencies were determined in a c ase-control study of 398 caucasian patients and 196 healthy controls. Patients had undergone angiography for investigation of coronary arter y disease and-ere evaluated for a history of myocardial infarction. Th e prevalence of the mutation was lower in patients with myocardial inf arction than without (32% vs. 50%), p = 0.0009 and than in controls (3 2% vs. 48%), p = 0.005. Patients possessing the mutation with a histor y of myocardial infarction had higher PAI-1 concentrations (mean, 27.9 vs. 16.7 ng/ml, p = 0.004) and the PAI-1 4G/4G genotype was commoner (43% vs. 26%, p = 0.03). There was no difference in PAI-1 4G/4G genoty pe (33% vs. 32%) and PAI-1 levels (mean, 21.0 vs. 20.9 ng/ml) in patie nts possessing wild type with MI compared to those without hll. These results indicate that the G-->T mutation coding for factor XIIIVa134Le u is protective against myocardial infarction and suggest a mechanism whereby elevated levels of PAI-1 may contribute to vascular risk.