title: Klotho locus, metabolic traits, and serum hemoglobin in hospitalized older patients: a genetic association analysis.
abstract: Klotho (KL) gene has been involved in severe alterations of physiological biochemical parameters leading to premature aging-like phenotypes and strikingly shortening lifespan. KL participates to the regulation of a number of intracellular biochemical pathways, including lipid profile and glucose metabolism. Aim of this study was to investigate the possible association between KL locus and biological parameters commonly accepted as indicators of the clinical status in hospitalized older patients. We genotyped the single-nucleotide polymorphisms (SNPs) rs9536314, rs1207568, and rs564481 at the KL locus in 594 hospitalized older patients (65-99 years), consecutively attending a geriatric ward, and tested the association of these KL variants with biological quantitative traits using analyses of covariance and genetic risk score models. Significant associations of rs9536314 with serum levels of hemoglobin, albumin, and high-density lipoprotein cholesterol (HDL-C) as well as significant associations of rs564481 with serum levels of hemoglobin, fasting insulin, and fasting glucose were observed. Gender-segregated analyses confirmed these associations, and suggested that the associations of KL genotypes with HDL-C, fasting glucose and fasting insulin levels may be driven by the female gender, while the association with serum levels of hemoglobin may be driven by the male gender. The association of KL genotypes with creatinine levels was found only in females, while the association with insulin-like growth factor-1 (IGF-1) and lymphocytes count (LC) was found only in males. The genetic risk score (GRS) models further confirmed significant associations among KL SNPs and hemoglobin, total cholesterol, and HDL-C. Gender-segregated analyses with the GRS-tagged approach confirmed the associations with HDL-C, fasting glucose, and fasting insulin levels in females, and with hemoglobin and LC in males. Our findings suggested that KL locus may influence quantitative traits such as serum levels of lipid, fasting glucose, albumin and hemoglobin in hospitalized older patients, with some gender differences suggested for creatinine, IGF-1 levels, and LC, thus being one of the genetic factors possibly contributing to age-related diseases and longevity.
authors.affiliation: Geriatric Unit and Gerontology-Geriatric Research Laboratory, Department of Medical Sciences, I.R.C.C.S. Casa Sollievo della Sofferenza, Viale Cappuccini 1, San Giovanni Rotondo, Foggia, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Paroni
authors.forename: Davide
authors.initials: D
authors.lastname: Seripa
authors.forename: Francesco
authors.initials: F
authors.lastname: Panza
authors.forename: Filomena
authors.initials: F
authors.lastname: Addante
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Copetti
authors.forename: Grazia
authors.initials: G
authors.lastname: D'Onofrio
authors.forename: Fabio
authors.initials: F
authors.lastname: Pellegrini
authors.forename: Luigi
authors.initials: L
authors.lastname: Fontana
authors.forename: Alberto
authors.initials: A
authors.lastname: Pilotto
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D001774:Blood Chemical Analysis; D001786:Blood Glucose / Q000032:analysis; D008076:Cholesterol, HDL / Q000097:blood*; D003430:Cross-Sectional Studies; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D015577:Geriatric Assessment / Q000379:methods*; D005966:Glucuronidase / Q000235:genetics*; D006454:Hemoglobins / Q000378:metabolism*; D006760:Hospitalization; D006801:Humans; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D000090265:Klotho Proteins; D008136:Longevity / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D018570:Risk Assessment; D012737:Sex Factors
chemical_list: D001786:Blood Glucose; D008076:Cholesterol, HDL; D006454:Hemoglobins; D007328:Insulin; D007334:Insulin-Like Growth Factor I; D005966:Glucuronidase; D000090265:Klotho Proteins