Association of Asn221Ser mutation in tissue factor pathway inhibitor-β with plasma total tissue factor pathway inhibitor level

Junko Ishikawa, Hiromi Okada, Hisao Kato, Satoshi Takeshita, Shigenori Honda, Tomio Kawasaki, Etsuji Suehisa, Hajime Tsuji, Seiji Madoiwa, Yoichi Sakata, Tetsuhito Kojima, Mitsuru Murata, Yasuo Ikeda, Yoshihiro Kokubo, Tomonori Okamura, Hitonobu Tomoike, Toshiyuki Miyata

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3 Citations (Scopus)

Abstract

Tissue factor pathway inhibitor (TFPI) is an anticoagulant protease inhibitor that inhibits the tissue factor-initiated blood coagulation cascade reactions. Based on these anticoagulant functions of TFPI, we hypothesized that genetic variations in TFPI may alter the TFPI expression or impair the anticoagulant function and could predispose persons to deep vein thrombosis (DVT). This study was undertaken to examine whether the genetic polymorphisms in TFPI are associated with the plasma TFPI levels and risk for DVT. We sequenced the entire coding regions of TFPI in 175 Japanese DVT patients and identified 12 genetic variants, including one missense mutation, Asn221Ser. The missense mutation occurred at the site presumably attached to the glycosylphosphatidylinositol anchor in the TFPI-p form. The allele frequency of the mutant Ser-coding allele of the Asn221Ser mutation was 8% in the Japanese general population consisting of 1684 individuals. The Asn221Ser mutation was significantly associated with the total TFPI levels (Asn/Asn, n = 108, total TFPI = 56.57 ± 0.88 ng/ml (mean ± SD) vs. Asn/Ser + Ser/Ser, n = 16, total TFPI = 63.44 ±.28 ng/ml, P= 0.0058). The genotype was not associated with the free TFPI level. This Asn221Ser mutation was not associated with DVT. Thus, the Asn221Ser mutation occurring in the TFPI-p form was associated with the total TFPI level, but not a risk for DVT. The absence of the putative glycosylphosphatidylinositol anchor in TFPI-β under pathological conditions remains to be studied. Blood Coagul Fibrinolysis 20:22-26

Original languageEnglish
Pages (from-to)22-26
Number of pages5
JournalBlood Coagulation and Fibrinolysis
Volume20
Issue number1
DOIs
Publication statusPublished - 2009 Jan

Keywords

  • Deep vein thrombosis
  • Glycosylphosphatidylinositol
  • Tissue factor pathway inhibitor

ASJC Scopus subject areas

  • Hematology

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    Ishikawa, J., Okada, H., Kato, H., Takeshita, S., Honda, S., Kawasaki, T., Suehisa, E., Tsuji, H., Madoiwa, S., Sakata, Y., Kojima, T., Murata, M., Ikeda, Y., Kokubo, Y., Okamura, T., Tomoike, H., & Miyata, T. (2009). Association of Asn221Ser mutation in tissue factor pathway inhibitor-β with plasma total tissue factor pathway inhibitor level. Blood Coagulation and Fibrinolysis, 20(1), 22-26. https://doi.org/10.1097/MBC.0b013e328304e0b9