Risk Factors for Asian Thrombophilia

亚洲人血栓形成倾向的危险因素

• 批准号: 13576031
• 负责人: HAMASAKI Naotaka
• 金额: $ 8.64万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13576031/
• 关键词: thrombophilia; Prolein S; polymorphism; gene analysis; tertiary structure of protein S; 血栓症の病因解析; ProteinC; ProteinS; 遺伝的背景

Although the constitutional background of Japanese thrombotic patients has not been well examined, coagulation factor V Leiden is not detected in Japanese patients suffering from thromboses. We have been investigating constitutional predispositions of patients suffering from deep vein thrombosis in the Japanese population. In the present study, we summarize our results of Japanese patients suffering from deep vein thrombosis.A surprisingly high frequency of Japanese patients suffering from deep vein thrombosis have reduced activity in the protein S/protein C anticoagulation system. Reduced activity in the protein S/protein C anticoagulation system was observed in 58% patients with deep vein thrombosis, while reduced activity of antithrombin was noted in 7% patients, a level consistent with the frequency in Caucasian patients. Gene analyses were performed on the factors associated with patients having reduced activities (10-12). Nineteen patients had mutated protein S genes, including 5 patients having protein S_<Tokushima>(K155E), 8 patients had mutated protein C genes, and two patients had mutated antithrombin genes.Our study indicates that the frequency of inherited protein S abnormalities in Japanese patients suffering from deep vein thrombosis is significantly high, ten times higher than the frequency in Caucasian patients, and that abnormality of the protein S/protein C anticoagulation system is a major risk factor for deep vein thrombosis in Japan. It is interesting to note that the frequency of factor V Leiden in Caucasian deep vein thrombosis patients is similar to that of gene mutations of the protein S/protein C anticoagulalion system in Japanese deep vein thrombosis patients.

虽然日本血栓形成患者的体质背景尚未得到很好的研究，凝血因子V莱顿是没有检测到日本患者患有血栓。我们一直在调查日本人群中深静脉血栓形成患者的体质倾向。在本研究中，我们总结了日本深静脉血栓形成患者的研究结果，发现日本深静脉血栓形成患者中蛋白S/蛋白C抗凝系统活性降低的频率非常高。在58%的深静脉血栓形成患者中观察到蛋白S/蛋白C抗凝系统活性降低，而在7%的患者中观察到抗凝血酶活性降低，这一水平与高加索患者的频率一致。对与活动减少的患者相关的因素进行基因分析（10-12）。19例患者有蛋白S基因突变，其中5例有蛋白S_<Tokushima>（K155 E），8例有蛋白C基因突变，2例有抗凝血酶基因突变，我们的研究表明，日本深静脉血栓患者中遗传性蛋白S异常的频率明显较高，是白种人的10倍，蛋白S/蛋白C抗凝系统的异常是日本深静脉血栓形成的主要危险因素。值得注意的是，高加索深静脉血栓形成患者中凝血因子V Leiden的频率与日本深静脉血栓形成患者中蛋白S/蛋白C抗凝系统的基因突变频率相似。

项目成果

Mutsuko Nakahara, Hiroko Iida, Michiyo Urata, Tsuneyoshi Yao, Naotaka Hamasaki: "A Novel Splice Acceptor Site Mutation of Protein S Gene in Affected Individuals with Type I Protein S Deficiency: Allelic Exclusion of the Mutant Gene"Throm. Res.. 101. 387-3

Mutsuko Nakahara、Hiroko Iida、Michiyo Urata、Tsuneyoshi Yao、Naotaka Hamasaki：“I 型蛋白 S 缺乏症患者中蛋白 S 基因的新型剪接受体位点突变：突变基因的等位基因排除”Throm。

Mutsuko Nakahara, Hiroko Iida, Michiyo Urata, Tsuneyoshi Yao, Naotaka Hamasaki: "A Novel Splice Acceptor Site Mutation of Protein S Gene in Affected Individuals with Type I Protein S Deficiency : Allelic Exclusion of the Mutant Gene"Throm. Res.. 101. 387-

Mutsuko Nakahara、Hiroko Iida、Michiyo Urata、Tsuneyoshi Yao、Naotaka Hamasaki：“I 型蛋白 S 缺乏症患者中蛋白 S 基因的新型剪接受体位点突变：突变基因的等位基因排除”Throm。

Hiroko Iida, Mutsuko Nakahara, KimihiroKomori, Keizo Sugimachi, Naokata Hamasaki: "Failure in the Detection of Aberrant mRNA from the Heterozygotic Splice Site Mutant Allele for Protein S in a Patient with Protein S Deficiency"Throm. Res.. 102. 187-196 (2

Hiroko Iida、Mutsuko Nakahara、KimihiroKomori、Keizo Sugimachi、Naokata Hamasaki：“在蛋白 S 缺乏症患者中检测到蛋白 S 杂合剪接位点突变等位基因的异常 mRNA 失败”Throm。

Iida h, Nakahara M, Komori K, Fujise M, Wakiyama M, Urata M, Kinoshita S, Tsuda H, Sugimachi K, Hamasaki N: "Failure in the Detection of Aberrant mRNA from the Heterozygotic Splice Site Mutant Allele for Protein S in a Patient with Protein S Deficiency"Th

Iida h、Nakahara M、Komori K、Fujise M、Wakiyama M、Urata M、Kinoshita S、Tsuda H、Sugimachi K、Hamasaki N：“未能检测到蛋白质 S 杂合剪接位点突变等位基因的异常 mRNA”

Oka, T., Murata, Y., Namba, M., Yoshimizu, T., Takao Toyomura, T., Yamamoto, A., Ge-Hong Sun-Wada, Hamasaki, N., Wada, Y., Futai, M: "a4, a Unique Kidney-specific Isoform of Mouse Vacuolar H^+-ATPase Subunit α"J. Biological Chemistry. 276(43). 40050-40054

Oka, T.、Murata, Y.、Namba, M.、Yoshimizu, T.、Takao Toyomura, T.、Yamamoto, A.、Ge-Hong Sun-Wada、Hamasaki, N.、Wada, Y.、Futai, M：“a4，小鼠液泡 H^+-ATP 酶亚基 α 的独特肾脏特异性亚型”J. 40050-40054。