KLOTHO polymorphisms and age-related outcomes in community-dwelling older subjects: The São Paulo Ageing & Health (SPAH) Study

• Published in: Scientific reports Vol. 10; no. 1; p. 8574
• Main Authors: Pereira, Rosa Maria R., Freitas, Thiago Quadrante, Franco, André Silva, Takayama, Liliam, Caparbo, Valeria F., Domiciano, Diogo S., Machado, Luana G., Figueiredo, Camille P., Menezes, Paulo R., Onuchic, Luiz Fernando, de Castro, Isac
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.05.2020; Nature Publishing Group
• Subjects: 692/308/2056; 692/53/2423; Aged; Aging; Aging - genetics; Alleles; Cardiovascular Diseases - genetics; Cardiovascular Diseases - mortality; Cardiovascular Diseases - pathology; Cerebral infarction; Death; Epidermal growth factor receptors; Gene expression; Genotypes; Geriatrics; Glucuronidase - genetics; Humanities and Social Sciences; Humans; Independent Living - statistics & numerical data; Klotho protein; Male; Mortality; multidisciplinary; Myocardial infarction; Osteoporosis; Polymorphism, Single Nucleotide; Prognosis; Risk Factors; Sarcopenia; Science; Science (multidisciplinary); Stroke - genetics; Stroke - mortality; Stroke - pathology; Survival Rate
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-65441-y

Defective KLOTHO gene expression in mice led to a syndrome resembling human ageing. This study evaluated three KLOTHO polymorphisms, namely G395A, C1818T, and C370S, in an elderly population (mean age of 73 years) and their associations with ageing-related outcomes (cardiovascular events, kidney function, osteoporosis, sarcopenia) and mortality. Estimated glomerular filtration rates (eGFR) was lower in subjects with 1818TT (P = 0.047) and 370SS (P = 0.046) genotypes. The 1818TT genotype (P = 0.006) and 1818T allele were associated with higher frequency of myocardial infarction (MI) (CC:1.7% vs. CT + TT:7.0%; P = 0.002). The 370SS genotype was associated with lower stroke frequency (P = 0.001). MI (OR 3.35 [95% CI: 1.29–8.74]) and stroke (OR 3.64 [95% CI: 1.48–8.97]) were associated with mortality. Regarding MI, logistic regression showed 1818T allele was a risk factor for death-related MI (OR 4.29 [95% CI: 1.60–11.52]; P = 0.003), while 370C was protective (OR 0.03 [95% CI: 0.01–0.08]; P < 0.001). Regarding stroke, the 395A and 370C alleles were protective factors (respectively: OR 0.28 [95% CI: 0.20–0.80]; P = 0.018; OR 0.10 [95% CI: 0.05–0.18]; P < 0.001). This is the first study to determine potential associations between common ageing-related outcomes/mortality and KLOTHO polymorphisms. The 1818T allele was a risk factor for MI-related death. The 395A and 370C alleles were protective factors for stroke-related death in elderly from community.