臨床検査53巻10号

2009年10月発行

今月の主題 血栓症と臨床検査 総説

先天性血栓性素因の遺伝子解析

著者： 宮田敏行¹

所属機関： ¹国立循環器病センター研究所病因部

ページ範囲：P.1123 - P.1128

　静脈血栓塞栓症(VTE)は多因子疾患であり，リスクとなる環境因子および遺伝因子が知られている．最近の研究により，日本人はVTEのリスクとしてプロテインS K196E変異を保有することが明らかとなってきた．日本人の55～60人に1人が本変異のヘテロ接合体であり，1.2～1.5万人に1人がホモ接合体と推定された．

参考文献

1) Miyata T, Kimura R, Kokubo Y, et al：Genetic risk factors for deep vein thrombosis among Japanese：importance of protein S K196E mutation. Int J Hematol　83：217-223, 2006

2) Okamoto A, Sakata T, Mannami T, et al：Population-based distribution of plasminogen activity and estimated prevalence and relevance to thrombotic diseases of plasminogen deficiency in the Japanese：the Suita Study. J Thromb Haemost　1：2397-2403, 2003

3) Kimura R, Honda S, Kawasaki T, et al：Protein S-K196E mutation as a genetic risk factor for deep vein thrombosis in Japanese patients. Blood　107：1737-1738, 2006

4) Kinoshita S, Iida H, Inoue S, et al：Protein S and protein C gene mutations in Japanese deep vein thrombosis patients. Clin Biochem　38：908-915, 2005

5) Yamazaki T, Sugiura I, Matsushita T, et al：A phenotypically neutral dimorphism of protein S：the substitution of Lys155 by Glu in the second EGF domain predicted by an A to G base exchange in the gene. Thromb Res　70：395-403, 1993

6) Hayashi T, Nishioka J, Shigekiyo T, et al：abnormal molecule with a substitution of Glu for Lys-155 in the second epidermal growth factor-like domain of protein S. Blood　83：683-690, 1994

7) Kimura R, Sakata T, Kokubo Y, et al：Plasma protein S activity correlates with protein S genotype but is not sensitive to identify K196E mutant carriers. J Thromb Haemost　4：2010-2013, 2006

8) Miyata T, Sato Y, Ishikawa J, et al. Prevalence of genetic mutations in protein S, protein C and antithrombin genes in Japanese patients with deep vein thrombosis. Thromb Res　124：14-18, 2009

9) Finazzi G, Caccia R, Barbui T：Different prevalence of thromboembolism in the subtypes of congenital antithrombin III deficiency：review of 404 cases. Thromb Haemost　58：1094, 1987

10) Bezemer ID, Bare LA, Doggen CJ, et al：Gene variants associated with deep vein thrombosis. JAMA　299：1306-1314, 2008

11) Tregouet DA, Heath S, Saut N, et al：Common susceptibility allele are unlikely to contribute as strongly as the FV and ABO loci to VTE risk：results from a GWAS approach.　Blood：2009［E-pub］