Polymorphisms of the tissue factor pathway inhibitor gene and the risk of restenosis after coronary angioplasty

Abstract

Intracoronary stent implantation is associated with a significantly lower risk of restenosis compared with balloon angioplasty. However, restenosis still occurs in some cases. Experimental studies suggest that the tissue factor pathway is involved in this phenomenon. We investigated a possible relationship between three previously identified polymorphisms of the tissue factor pathway inhibitor (TFPI) gene and restenosis in 443 patients who underwent angioplasty, with or without stent implantation. The effect of the intron 7-33T<--C polymorphism and that of the combined intron 7 and promoter genotype on plasma TFPI levels was also investigated in 58 healthy subjects. DNA analysis was performed by polymerase chain reaction amplification of genomic DNA extracted from white blood cells, followed by digestion with the restriction enzymes Hind III, Nde I and Mae III for the detection of promoter, intron 7 and exon IX polymorphisms, respectively. The minimal luminal diameter, percent stenosis, acute gain, late loss and loss index did not differ according to the genotype before, immediately after or 6 months after angioplasty, regardless of stent implantation. Interestingly, subjects with the intron 7 CC genotype had significantly higher total TFPI levels than those with the TT genotype before and after an enoxaparin injection. Moreover, subjects with the -287TT/Int7TT combined genotype had the lowest plasma TFPI levels. Despite significant variations in plasma TFPI levels, we found no evidence that three polymorphisms of the TFPI gene influence the risk of restenosis. These results do not exclude the possibility that other polymorphisms in the TFPI gene may influence this risk.

Regulation of Functions of Vascular Wall Cells by Tissue Factor Pathway Inhibitor

“…Their study did not support an association between TFPI polymorphism and acute coronary syndrome. The same authors 64,65 reported no link between this mutation and venous thromboembolic disease or restenosis after coronary angioplasty. Polymorphism in the promoter region of TFPI was not associated with the plasma level of TFPI or with venous thrombosis.…”

Polymorphisms in the tissue factor pathway inhibitor gene are not associated with ischaemic stroke

“…Miyata et al [17], however, found that this polymorphism was not related to total TFPI levels and its prevalence was unaltered among Japanese control individuals and patients with deep vein thrombosis. The CC genotype of the intron 7 C-33T polymorphism has been shown to be independently associated with a decrease in venous thromboembolism risk, but not with acute coronary events or restinosis after angioplasty [11,12,18]. In addition, this polymorphism is associated with increased total TFPI levels, but not free levels, in healthy control individuals [11,12].…”

“…In addition, this polymorphism is associated with increased total TFPI levels, but not free levels, in healthy control individuals [11,12]. Moatti et al [18] also demonstrated that the CC genotype is associated with higher total TFPI levels in women who suffered a deep vein thrombosis. Several studies have examined the V264M polymorphism [10,12,19], and while some have found an association with total TFPI none have linked it to coronary artery disease, venous thromboembolism or deep vein thrombosis.…”

Genetic susceptibility to thrombosis

“…The 399T>C polymorphism was found to be associated with lower plasma TFPI levels and increased plasma F1 + 2 levels, a marker of increased coagulation [21]. Similarly, a combination of 287T T within intron 7-33T T was associated with low plasma TFPI levels [22]. In addition, higher plasma TFPI levels were observed in patients carrying the -33CC polymorphism in intron 7 [23].…”