Thrombophilia in East Asian countries: are there any genetic differences in these countries?
Thrombophilia in East Asian countries: are there any genetic differences in these countries?
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DOI：
10.1186/s12959-016-0109-x
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发表时间：
2016
影响因子：
3.1
通讯作者：
Neki R
中科院分区：
文献类型：
--
作者：
Miyata T;Maruyama K;Banno F;Neki R
近年来，对东亚静脉血栓栓塞症（VTE）患者中三种抗凝蛋白（抗凝血酶、蛋白C（PC）和蛋白S（PS））先天性缺陷的遗传分析大大增加。PS-K196 E突变常在日本人群中发现，等位基因频率为0.86%，估计共有约10，000名日本人为纯合子。杂合子的PS抗凝活性范围为40 - 110%，平均抗凝活性比野生型个体低16%。最近已经开发了鉴定这种突变的携带者的特定测定方法。突变携带者在怀孕期间有血栓形成的风险，但似乎没有不良妊娠结局的风险。为了促进未来对这种突变及其与血栓形成的关系的研究，已经开发了具有PS K196 E突变的血栓形成倾向小鼠品系。我们发现PS-K196 E突变和杂合PS缺陷导致小鼠VTE增加，但不像因子V Leiden突变那样导致缺血性卒中加重。重要的是，PS-K196 E突变仅在日本人中发现。这表明，尽管东亚人群（包括日本人、中国人和韩国人）在地理和遗传上接近，但PS-K196 E突变似乎是日本人特有的，这表明该突变是最近发生的，并在日本人群中固定。在中国和韩国人群中已报道了一些易患VTE的复发性基因突变。虽然已知VTE的遗传背景在高加索血统人群和东亚人群之间存在差异，但即使在东亚人群中，一些复发性突变也不同。
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.