Polymorphisms of the tissue factor pathway inhibitor (TFPI) gene in patients with acute coronary syndromes and in healthy subjects - Impact of the V264M substitution on plasma levels of TFPI

Mutations of the gene encoding tissue factor pathway inhibitor (TFPI), an i nhibitor of TF-induced activation of the coagulation cascade, were screened far in 130 patients and 142 healthy controls to determine whether these va riants contribute to acute coronary syndromes or modify plasma TFPI levels. The following 3 new polymorphisms were identified: 384T-->C in exon IV, wh ich does not change the corresponding amino acid (tyrosine 57); -33C-->T in intron 7 (the T/T, C/T, and C/C genotypes were found in approximate to 50% , 40%, and 10% of subjects in both groups); and 874G-->A in exon IX (GTG--> ATG), which predicts a valine to methionine change (V264M) in the carboxy-t erminus tail of TFPI, The V264M polymorphism was found in 9.2% of the cases and 4.9% of the controls; the associated odds ratio (OR) for acute coronar y syndromes was 2.0 (95% confidence interval [CI], 0.7 to 5.1). The OR incr eased to 3.6 (95% CI, 0.8 to 15.7) and 3.2 (95% CI, 0.9 to 11.8) in nonsmok ers and patients without other risk factors, respectively. The possible lin k between the V264M polymorphism and coronary heart disease was checked in a large case-control study of myocardial infarction (Etude Cas-Temoins de l 'Infarctus du Myocarde [the ECTIM Study]). The results showed no link betwe en the V264M polymorphism and coronary syndromes. Interestingly, however, 5 patients heterozygous for the V264M polymorphism had significantly lower p lasma TFPI levels than did 13 patients with the most common genotype. Altho ugh our present results do not support an association between TEPI polymorp hisms and acute coronary syndromes, the possibility that 1 of them, especia lly the exon TX polymorphism, is associated with subtypes of myocardial inf arction or to evolutive particularities that were not assessed in this stud y, cannot be excluded and is currently being evaluated.