Identification of the novel signal peptide mutation, antithrombin-Siriraj causes type-I antithrombin deficiency in Thai patients
Identification of the novel signal peptide mutation, antithrombin-Siriraj causes type-I antithrombin deficiency in Thai patients
复制标题
新型信号肽突变的鉴定，抗凝血酶-Siriraj 导致泰国患者 I 型抗凝血酶缺乏
DOI：
10.1160/th05-03-0678
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发表时间：
2005
影响因子：
6.7
通讯作者：
V. Viprakasit
中科院分区：
文献类型：
--
作者：
Y. Chinthammitr;Worrawut Chinchang;T. Ruchutrakool;V. Viprakasit
血栓血液学2005;九十四：678-9先天性血栓前障碍显著促进自发性、复发性静脉血栓形成的发生，在东南亚人群中很少有文献记载。来自远东的研究，特别是在中国和日本人群中的研究（1-5）表明，很大比例的静脉血栓形成病例缺乏抗凝蛋白，特别是蛋白C、蛋白S和抗凝血酶（AT）。然而，这些促凝血抑制剂缺乏症的少数情况下，已被广泛的特点在分子水平上。这与西方国家的遗传风险模式形成对比，在西方国家，凝血因子V Leiden、凝血酶原20210 A等位基因和MTHFR（C667 T）突变是血栓形成的重要风险因素（6，7）。抗凝血酶是一种血浆丝氨酸蛋白酶抑制剂（丝氨酸蛋白酶抑制剂），是灭活促凝血因子（如凝血酶、因子Xa和XIa）的主要调节剂（8）。抗凝血酶基因突变引起的遗传缺陷导致复发性静脉血栓栓塞的风险显著增加（25-50倍）（9，10）。亚洲国家最近的研究表明，2-7%的静脉血栓形成患者存在抗凝血酶缺乏症的促血栓形成风险（1-5）。除了日本研究组报道的几种突变（11- 1 - 5）外，亚洲人群抗凝血酶缺乏症的分子缺陷尚不清楚。最近，我们分析了一个泰国家庭与抗凝血酶缺乏症，并确定了一个新的突变的潜在缺陷，这种丝氨酸蛋白酶抑制剂蛋白。
Thromb Haemost 2005; 94: 678–9 Congenital prothrombotic disorders contributing significantly to the development of spontaneous, recurrent venous thrombosis, are rarely documented in Southeast Asian populations. Studies from the Far East, especially in Chinese and Japanese populations (1–5), have suggested that a significant proportion of cases of venous thrombosis had deficiency of anticoagulant proteins, particularly protein C, protein S and antithrombin (AT). However, few cases of these procoagulant inhibitor deficiencies have been extensively characterized at the molecular level. This is in contrast to the pattern of genetic risks in Western countries where Factor V Leiden, the prothrombin 20210A allele and the MTHFR (C667T) mutation are important risk factors for thrombosis (6, 7). Antithrombin, a plasma serine protease inhibitor (serpin), is a major regulator inactivating procoagulant factors such as thrombin, factor Xa, and XIa (8). Inherited deficiency caused by antithrombin gene mutations results in a significantly increased risk (25–50 fold) of recurrent venous thromboembolism (9, 10). Recent studies from Asian countries have documented antithrombin deficiency as a prothrombophilic risk in 2–7% of patients with venous thrombosis (1–5).Apart from severalmutations reported by Japanese groups (11–15), the molecular defects underlying antithrombin deficiency inAsian populations is less elucidated. Recently, we analyzed a Thai family with antithrombin deficiency and identified a novel mutation underlying deficiency of this serpin protein.