Genetic polymorphisms and plasma levels of tissue factor and tissue factor pathway inhibitor in venous thromboembolism

Abstract

Tissue factor (TF) and tissue factor pathway inhibitor (TFPI) play important roles in coagulation. The aim of this study was to investigate the distributions of TF and TFPI polymorphisms in Koreans and to analyze the association of these genetic polymorphisms with plasma levels and development of venous thromboembolism (VTE). The polymorphisms TF 5466 A > G, TF -603 A > G, TFPI -287 T > C and TFPI -33 T > C were investigated in 40 Korean VTE patients and 40 age-matched and sex-matched controls by real-time PCR followed by melting curve analysis and DNA sequence analysis. Plasma levels of TF and TFPI were measured by enzyme-linked immunosorbent assay. The G allele of TF 5466 was not detected, and allelic frequencies of TF -603 G, TFPI -287 C and TFPI -33 C were 27.5, 67.5 and 16.2%, respectively. The distributions of TF and TFPI polymorphisms were not different between patients and controls. The presence of TF -603 G allele was correlated with low plasma TF levels (P = 0.029). Mean plasma TFPI levels were similar between TFPI genotypic groups. Although not statistically significant, plasma TF and TFPI levels were higher in patients than controls. The distributions of TF and TFPI polymorphisms in Koreans were considerably different from whites, suggesting ethnic variations. The TF -603 A > G polymorphism was significantly correlated with decreased plasma TF levels. Neither genetic polymorphisms in TF and TFPI nor their plasma levels seem to act as direct risk factors for VTE.

Association of TFPI polymorphisms rs8176592, rs10931292, and rs10153820 with venous thrombosis

“…[27] There were 8 studies with 976 cases and 1780 controls for TFPI rs8176592 polymorphism. All were case-control studies, including 3 venous thromboembolism (VTE) studies, [27,28,34] 3 DVT studies, [29,35,36] 1 venous thrombosis study, [32] and 1 cerebral venous thrombosis (CVT) study. [33] Subjects were sampled from France, Australia, Denmark, Norway, India, Korean, and China.…”

“…There were 5 studies with 453 cases and 795 controls for TFPI rs10931292 polymorphism. All were case-control studies, including three VTE studies, [28,31,34] 1 DVT study, [30] and 1 venous thrombosis study. [32] Subjects were sampled from Australia, England, China, Norway, and Korea.…”

“…For example, 5 studies report that TFPI rs8176592 polymorphism was related to the risk of venous thrombosis, [27,28,32,33,36] while 3 studies report it was not. [29,34,35] Amini reported that the TFPI rs10931292 polymorphism was related with venous thrombosis risk. [30] while 4 other studies reported that it was not related to the risk of venous thrombosis.…”

Circulating Tissue Factor Levels and Risk of Stroke

“…Circulating TF levels 40,41 and TF expression by blood cells 42,43 could be determined by genetic factors. We previously found that TF gene polymorphisms and haplotypes were associated with the risk of ischemic stroke at young age.…”

Identification of biomarkers of venous thromboembolism by bioinformatics analyses

“…In addition, a recent study suggested that tissue factor and tissue factor pathway inhibitor played key roles in coagulation and acted as direct risk factors for VTE. [ 13 ] Although progresses have been achieved for the pathogenesis of VTE, the genetic mechanisms are far from being understood. Determination of the recurrence risk factors for VTE is still a vital health concern.…”