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Dysfunction of protein C anticoagulant system, main genetic risk factor for venous thromboembolism in Northeast Asians

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Abstract

Venous thromboembolism (VTE) is a life-threatening medical disorder worldwide. A great deal of evidence suggests that prevalence of VTE varies significantly among ethnic populations, with consistently lower incidence found in Asians. While the distribution of genetic risk factors may vary among races, genetic risk factors can play a major role among individuals with different genetic backgrounds. Two clinically evaluated low-frequency genetic mutations that predispose to VTE—the factor V Leiden mutation and prothrombin G20210A mutation—are found predominantly in Caucasians, and virtually never in Asians. The findings of a recent genetic study of VTE in northeast Asians, which greatly advanced our knowledge in this area, indicate that the most frequent genetic risk factors for VTE in northeast Asians can be attributed to a dysfunction of the protein C anticoagulant system. Several low-frequency genetic mutations, PROS1 p.Lys196Glu in Japanese and PROC p.Arg189Trp and p.Lys193del in Chinese, are significantly associated with increased risk for VTE, with odds ratio more than 2 through the reduced protein C anticoagulant activity. Construction of a multifactorial model based on the genetic risk factors in the protein C anticoagulant system could facilitate genetic counseling for VTE risk in these populations. The influence of prevalent genetic mutations on the risk of VTE should be further investigated in Asian countries.

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Acknowledgments

This work was supported in part by grants-in-aid from the Ministry of Health, Labour, and Welfare of Japan; the Ministry of Education, Culture, Sports, Science, and Technology of Japan; the Japan Society for the Promotion of Science, and by grants from the Clinical Research Supportive Fund, General Hospital of Chinese People’s Liberation Army (No. 2012FC-TSYS-3042).

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  1. Institute of Geriatric Cardiology, General Hospital of Chinese People’s Liberation Army, Beijing, 100853, China

    Tong Yin

  2. Department of Molecular Pathogenesis, National Cerebral and Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka, 5658565, Japan

    Toshiyuki Miyata

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Correspondence to Toshiyuki Miyata.

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Yin, T., Miyata, T. Dysfunction of protein C anticoagulant system, main genetic risk factor for venous thromboembolism in Northeast Asians. J Thromb Thrombolysis 37, 56–65 (2014). https://doi.org/10.1007/s11239-013-1005-x

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