© 1999 American Heart Association, Inc.
Original Contributions |
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
From INSERM U479 and Service d'Hématologie et d'Immunologie (D.M., S.D., V.O., J.H., D.d.P.), Service de cardiologie A (P.S., M.C.A.), INSERM U409 (C.G., M.G., D.D.), Laboratoire de nutrition humaine, CHU Xavier Bichat (F.F.), and INSERM SC7 (O.P.), Paris, France; the MONICA Project, Bas-Rhin (D.A.), Lille (G.L.), and Haute-Garonne (J.-B.R.), France; and the MONICA Project, Belfast, Northern Ireland (A.E.).
Correspondence to D. de Prost, Hôpital Bichat, Service d'Hématologie et d'Immunologie Biologiques, 46, rue Henri Huchard, 75018 Paris, France. E-mail dominique.deprost{at}bch.ap-hop-paris.fr
Abstract—Mutations of the gene
encoding tissue factor pathway inhibitor (TFPI), an
inhibitor of TF-induced activation of the coagulation
cascade, were screened for in 130 patients and 142 healthy controls to
determine whether these variants contribute to acute coronary
syndromes or modify plasma TFPI levels. The following 3 new
polymorphisms were identified: 384T
C in exon IV, which does not
change the corresponding amino acid (tyrosine 57); -33CT in intron
7 (the T/T, C/T, and C/C genotypes were found in 
50%, 40%,
and 10% of subjects in both groups); and 874GA in exon IX
(GTGATG), which predicts a valine to methionine change (V264M) in
the carboxy-terminus 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 coronary syndromes was 2.0 (95%
confidence interval [CI], 0.7 to 5.1). The OR increased to 3.6 (95%
CI, 0.8 to 15.7) and 3.2 (95% CI, 0.9 to 11.8) in nonsmokers and
patients without other risk factors, respectively. The possible link
between the V264M polymorphism and coronary heart disease
was checked in a large case-control study of myocardial infarction
(Etude Cas-Témoins de l'Infarctus du Myocarde [the ECTIM
Study]). The results showed no link between the V264M polymorphism
and coronary syndromes. Interestingly, however, 5 patients
heterozygous for the V264M polymorphism had significantly lower
plasma TFPI levels than did 13 patients with the most common
genotype. Although our present results do not support an
association between TFPI polymorphisms and acute coronary
syndromes, the possibility that 1 of them, especially the exon IX
polymorphism, is associated with subtypes of myocardial infarction
or to evolutive particularities that were not assessed in this study,
cannot be excluded and is currently being evaluated.
Key Words: tissue factor pathway inhibitor • case-control studies • myocardial infarction • genetics
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