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Aging (Albany NY). 2018 Dec 31;11(1):104-114. doi: 10.18632/aging.101728.

A klotho gene single nucleotide polymorphism is associated with the onset of stroke and plasma klotho concentration.

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Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
Department of Prosthodontics, Gerodontology and Oral Rehabilitation, Osaka University Graduate School of Dentistry, Suita, Osaka 565-0871, Japan.
Department of Clinical Thanatology and Geriatric Behavioral Science, Osaka University Graduate School of Human Sciences, Suita, Osaka 565-0871, Japan.
Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Science, Kagoshima University, Kagoshima, Kagoshima 890-8544, Japan.
Division of Health Sciences, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
Contributed equally


Klotho protects against development of multiple age-related disorders, including cardiovascular diseases. We assessed whether a human klotho single nucleotide polymorphism (SNP) rs650439 is associated with the onset of stroke in hypertensive patients and plasma klotho concentration in the general population. Five hundred and twenty-three patients with hypertension were analyzed for both the presence of rs650439 and onset of stroke. We found that hypertensive patients with the TT genotype of rs650439 (n=52) had a higher incidence of stroke than those with AT (n=257) and AA (n=214) genotypes. Multivariate analysis indicated that the TT genotype was the only risk factor associated with increased incidence of stroke. Plasma klotho concentrations were measured in a general population (age=70±1 years) to assess the association between rs650439 and plasma klotho concentration. A significant trend was observed in the elderly population where plasma klotho concentration decreased as the T alleles in rs650439 increased. Subjects with a TT genotype had lower plasma klotho concentrations than those with AT+AA genotypes. In conclusion, TT genotype of klotho SNP (rs650439) is correlated with an increased incidence of stroke in hypertensive patients, and the mechanism underlying this correlation might involve the effect of rs650439 T allele on plasma klotho concentrations.


SNP; atherosclerosis; klotho; plasma klotho concentration; stroke

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