Genetic polymorphisms associated with thrombotic disorders in the Japanese population
Genetic polymorphisms associated with thrombotic disorders in the Japanese population
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日本人群中与血栓性疾病相关的基因多态性
DOI：
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
M. Murata
中科院分区：
文献类型：
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作者：
M. Murata
摘要遗传因素与许多环境危险因素共同参与血栓性疾病的易感性。冠状动脉疾病（CAD）和缺血性脑血管疾病是具有复杂多因素病因的典型人类属性。自从在高加索人群中发现两种血栓前突变（凝血因子V Leiden和凝血酶原G20210 A突变）以来，人们越来越多地认识到遗传因素对多因素疾病（如血栓形成）的作用。血浆同型半胱氨酸水平升高也是静脉和动脉血栓形成的危险因素。现在人们认为血栓形成倾向很常见，不仅限于罕见的疾病，例如生理性凝血抑制剂的先天性缺陷。长期以来，人们一直认为日本血栓性疾病的发病率较低，尽管在抗凝血酶、蛋白C或蛋白S缺乏症的患病率方面只有很小的差异。然而，与血栓形成相关的常见多态性的患病率存在关键差异。日本人不存在凝血因子V Leiden和凝血酶原突变，血小板整合素的多态性，即糖蛋白IIIa 33 Leu/Pro，在高加索人群中与动脉血栓形成的关系存在争议，在日本非常罕见。此外，一些临床相关因素的等位基因频率也不同，包括血小板和凝血因子。因此，需要对具有不同种族背景的每个人群进行单独研究。在许多涉及CAD、缺血性中风、外周动脉疾病和糖尿病血管并发症患者的等位基因关联研究中，我们发现遗传因素的影响根据所选病例和对照的特征而显着变化。研究发现，多种遗传风险因素的某种组合会大大增加中风的风险，特别是在年轻受试者中。许多基因参与决定个体间的性状变异，这些性状决定了疾病的发作和进展，以及对治疗的反应。预计没有单一基因会对血栓形成风险的确定产生重大影响。多态性标记的临床评价的最终目标是确定可以最好地预防疾病或对干预措施反应最好的个体亚组。
Abstract Genetic factors in combination with a number of environmental risk factors are involved in a predisposition to thrombotic disorders. Coronary artery disease (CAD) and ischemic cerebrovascular disease are typical human attributes that have a complex multifactorial etiology. There has been an increased awareness of the contribution of inherited factors for multifactorial disorders like thrombosis since the discovery of two prothrombotic mutations, the factor V Leiden and the prothrombin G20210A mutations, prevalent in Caucasian populations. Elevated plasma levels of homocysteine also constitute a risk factor for venous and arterial thrombosis. Thrombophilia is now thought to be common, not limited to rare conditions such as congenital deficiencies of the physiologic coagulation inhibitors. It has long been thought that Japan has a lower incidence of thrombotic diseases, although there are only small differences in the prevalence of antithrombin, protein C, or protein S deficiencies. There are, however, critical differences in the prevalence of common polymorphisms relevant to thrombosis. The factor V Leiden and prothrombin mutations are absent in the Japanese, and a polymorphism of a platelet integrin, the glycoprotein IIIa 33Leu/Pro, which has a controversial relationship with arterial thrombosis in Caucasian populations, is very rare in Japan. Also, allele frequencies of some clinically relevant factors are different, including platelets and blood coagulation factors. Thus, a separate study is needed for each population with a distinct ethnic background. In a number of allelic association studies involving patients with CAD, ischaemic stroke, peripheral artery disease, and vascular complications of diabetes, we found that the effect of genetic factors varied significantly depending on the characteristics of the cases and controls selected. A certain combination of multiple genetic risk factors was found to greatly increase the risk of stroke, particularly in young subjects. Many genes are involved in determining the inter-individual variation in traits that define the onset and progression of disease, as well as the response to treatment. No single gene is expected to have a major impact on the determination of the risk of thrombosis. The ultimate goal of the clinical appreciation of polymorphic markers is to identify subgroups of individuals in which the disease can be best prevented, or who respond best to interventions.
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糖蛋白 (GP) Ibalpha 基因的 Kozak 序列多态性是血小板 GP Ib-IX-V 复合物质膜水平的主要决定因素。
影响因子：
20.3
作者：
Afshar-Kharghan,V;Li,CQ;Khoshnevis-Asl,M;López,JA
通讯作者：
López,JA
影响因子：
15.9
作者：
IKEDA, Y;HANDA, M;RUGGERI, ZM
通讯作者：
RUGGERI, ZM
影响因子：
158.5
作者：
Weiss, EJ;Bray, PF;GoldschmidtClermont, PJ
通讯作者：
GoldschmidtClermont, PJ
影响因子：
8.7
作者：
Feng, DL;Lindpaintner, K;Tofler, GH
通讯作者：
Tofler, GH
人糖蛋白 Ib α 的多态性是由粘蛋白样巨糖肽区域中 13 个氨基酸序列的不同数量的串联重复引起的。
DOI：
--
发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
López,JA;Ludwig,EH;McCarthy,BJ
通讯作者：
McCarthy,BJ