title: The association of protein S Tokushima-K196E with a risk of deep vein thrombosis.
abstract: Deep vein thrombosis (DVT) is a multifactorial disease caused by acquired risk factors such as a bed rest, surgery and malignancies. Although the factor V Leiden and the prothrombin-20210G>A mutation do not exist in Japanese populations, a mutation in protein S (PS) Tokushima (K196E) has been attracting attention in Japan. In this study, the genetic contribution of PS Tokushima (K196E) was evaluated in 60 Japanese patients with thrombosis in comparison to 234 healthy volunteers and 88 patients without thrombosis. Genes associated with the response to warfarin, cytochrome P450 2C9 (CYP2C9), vitamin K epoxide reductase complex subunit 1 (VKORC1), and γ-glutamyl carboxylase (GGCX) were also investigated simultaneously. PS Tokushima (K196E) was detected in 6 patients with thrombosis, in 3 without thrombosis and in 3 healthy volunteers, indicating that there is a high frequency of the PS Tokushima (K196E). There were no significant differences of CYP2C9, VKORC1 or GGCX between the patients with and without DVT. Therefore, PS Tokushima (K196E) is an important genetic risk factor for DVT in the Japanese population.
authors.affiliation: Central Laboratory, Mie University Graduate School of Medicine, Tsu, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ikejiri
authors.forename: Hideo
authors.initials: H
authors.lastname: Wada
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sakamoto
authors.forename: Naohiko
authors.initials: N
authors.lastname: Ito
authors.forename: Junji
authors.initials: J
authors.lastname: Nishioka
authors.forename: Kaname
authors.initials: K
authors.lastname: Nakatani
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tsuji
authors.forename: Norikazu
authors.initials: N
authors.lastname: Yamada
authors.forename: Mashio
authors.initials: M
authors.lastname: Nakamura
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ito
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nobori
mesh_terms: D016022:Case-Control Studies; D005787:Gene Frequency; D056726:Genetic Association Studies; D006801:Humans; D007564:Japan / Q000453:epidemiology; D020125:Mutation, Missense; D017293:Protein S / Q000235:genetics*; D012307:Risk Factors; D020246:Venous Thrombosis / Q000209:etiology / Q000235:genetics*
chemical_list: D017293:Protein S; C083863:protein S Tokushima
references.citation: Thromb Res. 2007;120(2):181-6
references.pmid: 17049586
references.citation: Br J Haematol. 2004 Jun;125(5):647-54
references.pmid: 15147381
references.citation: Blood Coagul Fibrinolysis. 2001 Mar;12(2):95-9
references.pmid: 11302483
references.citation: Nature. 1994 May 5;369(6475):64-7
references.pmid: 8164741
references.citation: J Thromb Haemost. 2004 Jun;2(6):1012-3
references.pmid: 15140145
references.citation: N Engl J Med. 1995 Apr 6;332(14):912-7
references.pmid: 7877648
references.citation: Thromb Res. 1995 Jan 1;77(1):1-43
references.pmid: 7701473
references.citation: J Hum Genet. 2006;51(3):249-253
references.pmid: 16432637
references.citation: Blood. 2000 Mar 15;95(6):1935-41
references.pmid: 10706858
references.citation: Br J Haematol. 2004 Jul;126(2):219-25
references.pmid: 15238143
references.citation: Blood. 2006 Feb 15;107(4):1737-8
references.pmid: 16461766
references.citation: Thromb Res. 2000 Dec 1;100(5):367-71
references.pmid: 11150577
references.citation: Ann Clin Biochem. 1999 Jul;36 ( Pt 4):423-32
references.pmid: 10456203
references.citation: Thromb Haemost. 2000 Nov;84(5):918
references.pmid: 11127877
references.citation: Pharmacogenet Genomics. 2006 Feb;16(2):101-10
references.pmid: 16424822
references.citation: Blood. 1994 Feb 1;83(3):683-90
references.pmid: 8298131
references.citation: Biochim Biophys Acta. 1995 Dec 12;1272(3):159-67
references.pmid: 8541347
references.citation: Thromb Haemost. 1991 Jul 12;66(1):49-61
references.pmid: 1833851
references.citation: Clin Biochem. 2005 Oct;38(10):908-15
references.pmid: 15978566