Association Analysis of Tissue Factor Pathway Inhibitor Polymorphisms and Haplotypes with Osteonecrosis of the Femoral Head in the Korean Population

• Published in: Molecules and cells Vol. 26; no. 5; pp. 490 - 495
• Main Authors: Dai, Xue Lian (Kyungpook National University Hospital, Daegu, Republic of Korea), Hong, J.M. (Kyungpook National University Hospital, Daegu, Republic of Korea), Oh, B.S. (National Institute of Health, Seoul, Republic of Korea), Cho, Y.S. (National Institute of Health, Seoul, Republic of Korea), Lee, J.Y. (National Institute of Health, Seoul, Republic of Korea), Park, E.K. (Kyungpook National University Hospital, Daegu, Republic of Korea), Kim, C.Y. (Yeungnam University, Daegu, Republic of Korea), Kim, S.Y. (Kyungpook National University Hospital, Daegu, Republic of Korea), E-mail: syukim@knu.ac.kr, Kim, T.H. (Kyungpook National University Hospital, Daegu, Republic of Korea), E-mail: archion@knu.ac.kr
• Format: Journal Article
• Language: English
• Published: United States 한국분자세포생물학회 30.11.2008
• Subjects: Asian People - genetics; Case-Control Studies; Female; femoral head; Femur Head Necrosis - genetics; Gene Frequency; Genetic Predisposition to Disease; Haplotypes; Humans; Korea; Linkage Disequilibrium - genetics; Lipoproteins - genetics; Male; osteonecrosis; POLIMORFISMO; POLYMORPHISM; Polymorphism, Single Nucleotide - genetics; POLYMORPHISME; TFPI; THROMBOSE; THROMBOSIS; TROMBOSIS; 생물학; Korea
• ISSN: 1016-8478; 0219-1032
• DOI: 10.1016/S1016-8478(23)14028-3

Thrombophilia and hypofibrinolysis have been implicated in the pathogenesis of osteonecrosis of the femoral head (ONFH). Tissue factor pathway inhibitor (TFPI), a multivalent protease inhibitor, is an important regulator of the tissue factor-mediated blood coagulation pathway. Mutations of the TFPI gene can increase the risk of thrombin generation and venous thrombosis. The aim of this study was to evaluate the association of TFPI gene polymorphisms with ONFH. All exons and their boundaries of the TFPI gene, including the -1,500 bp promoter region, were directly sequenced in 24 Korean individuals and four sequence variants were identified. These four polymorphisms [-51096 G greater than A (C-399T), -50984A greater than G (T-287C), + 24999A greater than G (Int7 -33T greater than C), + 37339T greater than A] were genotyped in 474 ONFH patients and 349 control subjects. The association of genotyped SNPs with ONFH was not found in the present study. The haplotype AAAT of TFPI was significantly associated with total, alcohol-induced, and idiopathic ONFH (p = 0.003, 0.021, and 0.007, respectively), and the haplotype GAAT was significantly associated with total and alcohol ONFH (p = 0.022 and 0.009, respectively). In addition, a new SNP + 37339 T greater than A in the 3'-UTR of the TFPI gene, was found in the Korean population. To date, this study is the first to show that haplotypes of the TFPI gene are associated with an increased susceptibility for ONFH. The results suggest that genetic variations in TFPI may play an important role in the pathogenesis and risk factors of ONFH.