A new T-287C polymorphism in the 5 ' regulatory region of the tissue factor pathway inhibitor gene - Association study of the T-287C and C-399T polymorphisms with coronary artery disease and plasma TFPI levels

Tissue factor pathway inhibitor (TFPI) is an important regulator of the ext rinsic blood coagulation pathway. We screened the untranslated 5' region of the TFPI gene for polymorphisms and investigated their possible involvemen t in arterial thrombosis. The allele frequencies of a new polymorphism, loc ated 287 base pairs upstream of the transcription start site (T-287C), and that of the previously described C-399T polymorphism, were similar in cases and controls. In controls, the -287C allele was associated with significan tly higher levels of total TFPI antigen, arguing for an effect of this poly morphism on TFPI gene expression. In controls, the C-399T polymorphism did not alter TFPI levels. In the cases, however, decreased total and post-hepa rin free TFPI levels and increased F1+2 levels were significantly associate d with the -399T allele. These findings suggest that the T-287C and C-399T polymorphisms are not associated with an increased risk of coronary heart d isease, a result which should be confirmed by a larger study. However, thei r influence on outcome, or a link with subtypes of acute coronary syndromes , cannot be excluded.