Department of Neurochemistry, National Institute of Mental Health and Neuro Sciences (NIMHANS), Bangalore 560029, India.
Biochem Biophys Res Commun. 2010 Dec 17;403(3-4):412-6. doi: 10.1016/j.bbrc.2010.11.045. Epub 2010 Nov 17.
Genetic variants of Klotho have been reported to be associated with human longevity and atherosclerotic vascular events and risk factors. However, very few studies have explored their association with ischemic stroke. We hypothesized that the functional KL-VS and the exonic C1818T variants of Klotho gene may be associated with ischemic stroke in Indian population. We enrolled a total of 460 patients with ischemic stroke and 574 age- and gender-matched controls for the study. Genotyping was done by polymerase chain reaction and restriction fragment length polymorphism. Contrary to other Asian reports, KL-VS variant was polymorphic in our population, with a frequency distribution similar to that of Caucasians. The frequency distribution of the C1818T variant was similar to previously reports in Asians. A differential effect of age on association of Klotho KL-VS variant with ischemic stroke was observed. In subjects aged ≤40 years, the KL-VS homozygotes, 352FF and 352VV, had ~1.5-fold (OR=1.57; 95% CI: 1.02-2.40, p=0.038) and ~3-fold (OR=3.29; 95%CI: 1.02-10.56, p=0.046) higher risk of stroke compared to heterozygotes, whereas in the older group (aged >40 years) no significant association was observed. The C1818T variant was not associated with ischemic stroke. We conclude that KL-VS homozygosity could contribute to early-onset stroke in India. Larger studies in other ethnic populations are warranted to determine the role of these gene variants in the etiology of stroke occurring in the young.
Klotho 基因的遗传变异与人类长寿和动脉粥样硬化血管事件及危险因素有关。然而，很少有研究探讨其与缺血性中风的关系。我们假设 Klotho 基因的功能 KL-VS 和外显子 C1818T 变异与印度人群的缺血性中风有关。我们共纳入了 460 例缺血性中风患者和 574 名年龄和性别匹配的对照者进行研究。基因分型采用聚合酶链反应和限制性片段长度多态性分析。与其他亚洲人群的报道相反，KL-VS 变异在我们的人群中是多态的，其频率分布与白种人相似。C1818T 变异的频率分布与亚洲人群的先前报道相似。Klotho KL-VS 变异与缺血性中风的相关性随年龄的不同而不同。在年龄≤40 岁的患者中，KL-VS 纯合子 352FF 和 352VV 患中风的风险约为杂合子的 1.5 倍（OR=1.57；95%CI：1.02-2.40，p=0.038）和 3 倍（OR=3.29；95%CI：1.02-10.56，p=0.046）。而在年龄较大的组（>40 岁），未观察到显著相关性。C1818T 变异与缺血性中风无关。我们的结论是 KL-VS 纯合子可能导致印度早发性中风。需要在其他种族人群中进行更大规模的研究，以确定这些基因变异在年轻人中风发病机制中的作用。
