Thrombophilia in East Asian countries: are there any genetic differences in these countries?

Thrombosis Journal - Tập 14 - Trang 123-128 - 2016
Toshiyuki Miyata, Keiko Maruyama1, Fumiaki Banno2, Reiko Neki3,4
1Department of Molecular Pathogenesis, National Cerebral and Cardiovascular Center, Suita, Japan
2Department of Food and Nutrition, Koriyama Women’s University, Koriyama, Japan
3Division of Counseling for Medical Genetics, National Cerebral and Cardiovascular Center, Suita, Japan
4Department of Perinatology and Gynecology, National Cerebral and Cardiovascular Center, Suita, Japan

Tóm tắt

In recent years, genetic analyses of congenital deficiencies of three anticoagulant proteins, antithrombin, protein C (PC) and protein S (PS), in East Asian patients with venous thromboembolism (VTE) have greatly increased. The PS-K196E mutation is often identified in the Japanese population with an allelic frequency of 0.86 %, and a total of approximately 10,000 Japanese are estimated to be homozygotes. The heterozygotes show PS anticoagulant activities ranging from 40 to 110 %, and 16 % lower mean anticoagulant activity than that in wild-type individuals. Specific assay methods to identify carriers of this mutation have recently been developed. The mutation carriers are at risk of thrombosis during pregnancy but do not appear to be at risk for adverse pregnancy outcomes. To promote future research into this mutation and its relation to thrombosis, a thrombosis-prone mouse strain with the PS K196E mutation has been developed. We found the PS-K196E mutation and the heterozygous PS-deficiency in mice caused increased VTE, but did not cause aggravation of ischemic stroke, unlike factor V Leiden mutation. Importantly, the PS-K196E mutation is only identified in Japanese. This suggests that although East Asian populations including Japanese, Chinese, and Koreans are geographically and genetically close, the PS-K196E mutation seems to be Japanese-specific, suggesting that the mutation is a recent occurrence and fixed within the Japanese population. Some recurrent genetic mutations predisposing to VTE have been reported in Chinese and Korean populations. Although the genetic background for VTE is known to differ between populations with Caucasian descent and East Asian populations, some of the recurrent mutations differ even within the East Asian populations.

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Thrombosis Journal

Tập 14

123-128

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