Abstract
BackgroundTissue factor pathway inhibitor (TFPI) is the main physiological inhibitor of TF-induced blood coagulation process, and may play essential roles in the pathogenesis of major adverse cardiac events. This study was designed to determine whether the variation of TFPI was related with coronary artery disease (CAD) in the Han Chinese populations.MethodsA total of 1271 patients with coronary atherosclerosis and 1287 normal individuals from northern China were enrolled in the present study. Four tagging single-nucleotide polymorphisms (SNPs) (rs7586970, rs6434222, rs10153820 and rs8176528) from TFPI were selected and genotyped by direct sequencing. And the genotypes of the above SNPs were determined in all these participants.ResultsIn the populations from Beijing and Harbin, no significant case-control differences in the frequencies of TFPI polymorphism (rs10153820 and rs8176528) were observed between CAD patients and controls. Meanwhile, two SNPs of TFPI (rs7586970 and rs6434222) were found to be associated with CAD in both groups. In stratified analyses based on gender, smoking, hypertension, diabetes mellitus and hyperlipidemia, we further determined that the investigated genetic variations of the TFPI genes seemed to be related with diabetes mellitus in CAD patients.ConclusionsGenetic variations of the TFPI genes seem to be related with CAD, which likely cooperate with metabolic risk factor (diabetes mellitus) and play critical roles in the pathogenesis of coronary artery disease.
Highlights
Tissue factor pathway inhibitor (TFPI) is the main physiological inhibitor of tissue factor (TF)-induced blood coagulation process, and may play essential roles in the pathogenesis of major adverse cardiac events
We found that frequencies of rs7586970 and rs6434222 showed significant difference in Chinese coronary artery disease (CAD) patients, indicating that the information of the TFPI gene polymorphism was helpful for evaluating the risk of developing coronary heart disease in Han Chinese
We found that the investigated genetic polymorphisms of the TFPI genes seemed to be related with diabetes mellitus in our enrolled CAD Han Chinese patients
Summary
Tissue factor pathway inhibitor (TFPI) is the main physiological inhibitor of TF-induced blood coagulation process, and may play essential roles in the pathogenesis of major adverse cardiac events. Rupture or erosion of atherosclerotic plaques or endothelial cell damage can cause exposure of subendothelial procoagulants such as tissue factor (TF) to circulating blood, followed by the activation of the coagulation process, leading to thrombin formation and subsequent acute coronary occlusion [4]. Heterozygous TFPI deficiency in atherosclerosis-prone mice exhibited a greater atherosclerotic burden, increased plaque tissue factor activity and decreased time to occlusive thrombosis after photochemical vascular injury [10, 11]. These studies indicate that TFPI attenuates TF activity and acts as a potential modulator of both atherosclerosis and arterial thrombosis
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