Kim Younyoung, Kim Jin-Hyuck, Nam Yu Jin, Kong Minyoung, Kim Yun Joong, Yu Kyung-Ho, Lee Byung-Chul, Lee Chaeyoung
Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Kyonggi-do, South Korea.
Neurosci Lett. 2006 Oct 30;407(3):189-94. doi: 10.1016/j.neulet.2006.08.039. Epub 2006 Sep 14.
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+GA 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.
衰老抑制基因α-klotho是血管疾病的一个候选因素，因为其缺陷会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α-klotho基因多态性与缺血性中风的关联。我们在α-klotho基因的启动子和外显子中搜索序列变异。对于关联研究，在对照受试者以及缺血性中风和血管性痴呆患者中对选定的变异进行基因分型。根据急性中风治疗中Org 10172试验（TOAST）对缺血性中风亚型进行分类，进一步研究其与缺血性中风的关联。未观察到G-395A和C1818T与缺血性中风和血管性痴呆有显著关联（P>0.05）。对缺血性中风亚型的分析显示，G-395A的A等位基因增加了心源性栓塞性中风（CE）的风险（比值比[OR]=2.60；P=0.006），并且携带A等位基因的受试者在显性（AA+GA对GG；OR=2.50；P=0.046）和隐性（AA对GA+GG；OR=6.52；P=0.007）模型中都易患CE。按性别对数据进行进一步分析表明，G-395A与CE的关联仅存在于女性中（A对G；OR=4.33；P=0.002，AA+GA对GG；OR=5.68；P=0.014，以及AA对GA+GG；OR=9.07；P=0.012），但在男性中这种显著性消失（P>0.05）。α-klotho基因中G-395A的序列变异可能是女性CE的一个遗传风险因素。
