Klotho is a genetic risk factor for ischemic stroke caused by cardioembolism in Korean females
Klotho is a genetic risk factor for ischemic stroke caused by cardioembolism in Korean females
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DOI：
10.1016/j.neulet.2006.08.039
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发表时间：
2006-10-30
影响因子：
2.5
通讯作者：
Lee, Chaeyoung
中科院分区：
文献类型：
--
作者：
Kim, Younyoung;Kim, Jin-Hyuck;Lee, Chaeyoung
衰老抑制基因klotho是血管疾病的候选因子，因为其缺陷导致内皮依赖性血管舒张受损和血管生成受损。我们研究了klotho基因多态性与缺血性卒中的关系。我们在klotho基因的启动子和外显子中寻找序列变异。在相关性研究中，对对照组和缺血性中风及血管性痴呆患者进行了基因分型。进一步研究了与缺血性卒中的相关性，并根据急性卒中治疗试验（吐司）对其亚型进行了分类。G-395 A和C1818 T与缺血性脑卒中和血管性痴呆的发生无明显相关性（P > 0.05）。对缺血性卒中亚型的分析显示，G-395 A的A等位基因增加了心源性卒中的风险（CE，OR = 2.60; P = 0.006），携带A等位基因的受试者在两种显性遗传中均易患CE。（AA + GA对GG; OR = 2.50; P = 0.046）和隐性（AA对GA + GG; OR = 6.52; P = 0.007）模型。进一步按性别划分的数据分析显示，G-395 A与CE的关联仅存在于女性中（A对G; OR = 4.33; P = 0.002），AA + CA对GG; OR = 5.68; P = 0.014，AA对GA + GG; OR = 9.07; P = 0.012），但男性无显著性差异（P > 0.05）。klotho基因G-395 A序列变异可能是女性CE的遗传危险因素。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
An aging-suppressor gene, klotho, is a candidate factor for vascular disease because its deficiency leads to impaired endothelium-dependent vasodilation and impaired angiogenesis. We investigated the association of polymorphisms in klotho with ischemic stroke. We searched for sequence variants in promoter and exons of klotho gene. For the association study, selected variants were genotyped in control subjects and in patients with ischemic stroke and vascular dementia. The association with ischemic stroke was further investigated with its subtypes classified based on Trial of Org 10172 in Acute Stroke Treatment (TOAST). No significant association was observed for both G-395A and C1818T with ischemic stroke and vascular dementia (P > 0.05). The analysis with subtypes of ischemic stroke revealed the associations that the A allele of G-395A increased the risk of cardioembolic stroke (CE, OR = 2.60; P = 0.006), and subjects carrying the A allele were susceptible to CE in both of dominant (AA + GA versus GG; OR = 2.50; P = 0.046) and recessive (AA versus GA + GG; OR = 6.52; P = 0.007) models. Further analysis of data partitioned by gender showed that the associations of G-395A with CE only existed in women (A versus G; OR = 4.33; P = 0.002), AA + CA versus GG; OR = 5.68; P = 0.014, and AA versus GA + GG; OR = 9.07; P = 0.012), but the significance disappeared in men (P > 0.05). The sequence variant of G-395A in klotho might be a genetic risk factor for CE in females. (c) 2006 Elsevier Ireland Ltd. All rights reserved.