Klotho is a genetic risk factor for ischemic stroke caused by cardioembolism in Korean females.
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.
Kim
Younyoung
Y
Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Kyonggi-do, South Korea.
Kim
Jin-Hyuck
JH
Nam
Yu Jin
YJ
Kong
Minyoung
M
Kim
Yun Joong
YJ
Yu
Kyung-Ho
KH
Lee
Byung-Chul
BC
Lee
Chaeyoung
C
D000208:Acute Disease; D000368:Aged; D002545:Brain Ischemia / Q000150:complications / Q000235:genetics*; D015140:Dementia, Vascular / Q000235:genetics; D004617:Embolism / Q000150:complications*; D005260:Female; D005838:Genotype; D005966:Glucuronidase / Q000235:genetics*; D006331:Heart Diseases / Q000150:complications*; D006801:Humans; D000090265:Klotho Proteins; D007723:Korea; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D020521:Stroke / Q000209:etiology / Q000235:genetics*
D005966:Glucuronidase; D000090265:Klotho Proteins