Gender differences of polymorphisms in the TF and TFPI genes, as related to phenotypes in patients with coronary heart disease and type-2 diabetes

Patients with angiographically verified CHD (n = 1001; 22% women, 20% diabetics), and 204 healthy controls (28% women), were included. The investigated SNPs were: TF -1812C/T and TF -603A/G in the 5'upstream region, TF 5466A/G in intron 2, TFPI -399C/T and TFPI -287T/C in the 5'upstream region and the TFPI -33T/C in intron 7.No significant differences in frequencies between the CHD population and the controls of any polymorphisms were observed. In the CHD population, the TF 5466 A/G SNP were significantly more frequent in women as compared to men (p < 0.001). The TF-1812C/T and the TF-603A/G SNPs were significantly more frequent in women without type-2 diabetes compared to those with diabetes (p < 0.018, both), and the heterozygous genotypes were associated with significantly lower TF plasma levels compared to the homozygous genotypes (p < 0.02, both).The TFPI-399C/T and the TFPI-33T/C SNPs were associated with lower and higher TFPI total antigen levels, respectively (p < 0.001, both).Genetic variations in the TF and TFPI genes seem to be associated with gender and type-2 diabetes, partly affecting their respective phenotypes.Tissue factor (TF) and its endogenous inhibitor, tissue factor pathway inhibitor (TFPI) are the main regulators of the initiation of the coagulation process, important in atherothrombosis. Injury of the vessel wall and rupture of an atherosclerotic plaque lead to exposure of TF to circulating blood, followed by an activation of the haemostatic system. In addition, blood-borne, or soluble TF (TF) from micro particles and monocytes may represent thrombogenic potential [1]. TFPI is the main regulator in the initial step of the coagulation cascade mediated by TF, by binding to coagulation factors Xa, VIIa and TF forming an inactive complex [2,3]. TFPI, mainly produced by the endothelium [4], is predominantly associated with lipoproteins in the blood [2,5] or is endothelial-bound [6], whereas a small portion circulates as free molecules. Enhanced TF