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

Abstract

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.

No significant association of serum klotho concentration with blood pressure and pulse wave velocity in a Chinese population

“…A growing body of evidence has suggested that some single nucleotide polymorphisms in the klotho gene were correlated with the circulating klotho levels and the susceptibility to hypertension 24 , salt hypertension 8 , and coronary artery disease 25 as well as the onset of stroke 26 . Though we did not find a significant relationship between the serum klotho concentrations, blood pressure, and PWV, we cannot exclude the possibility that genetic polymorphisms of the klotho gene may be associated with blood pressure and arterial stiffness.…”

Protective association of Klotho rs495392 gene polymorphism against hepatic steatosis in non-alcoholic fatty liver disease patients

“…46 For instance, another intronic variant in KL rs650439 was suggested to be associated with plasma Klotho concentration. 47 In addition, previous large eQTL meta-analysis in whole blood suggested the SNP rs495392 as cis-eQTL signal for the expression of KL gene. 17 Although the present study does not have the information on serum Klotho concentrations, the expression of sKL in liver tissues was examined.…”

El gran papel de Klotho

“…Dado el papel de los fgf endocrinos en un rango de respuestas fisiológicas, incluidos minerales y energía metabólica, respuestas al estrés y trastornos relacionados con el envejecimiento, agonistas y antagonistas de estas hormonas son posibles candidatos terapéuticos para diversos trastornos (19,20). Los datos estructurales obtenidos para endocrina espera que los fgf y las proteínas Klotho se aceleren (21,22,23).…”

“…βKlotho ha sido cristalizado con y sin fgf21. De manera similar a la interacción de αKlotho con fgf23, βKlotho interactúa directamente con el término c de fgf21 (5,(15)(16)(17)(18); sin embargo, no se pudo resolver la estructura de algunas regiones de este complejo, incluida la rba de αKlotho (19)(20)(21)(22)(23).…”