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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.

SUBMITTER: Paroni G

PROVIDER: S-EPMC3682056 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Klotho locus, metabolic traits, and serum hemoglobin in hospitalized older patients: a genetic association analysis.

Paroni Giulia G Seripa Davide D Panza Francesco F Addante Filomena F Copetti Massimiliano M D'Onofrio Grazia G Pellegrini Fabio F Fontana Luigi L Pilotto Alberto A

Age (Dordrecht, Netherlands) 20110622 4

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. ...[more]

PMID: 21695423

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Project description:ObjectiveHyperhomocysteinemia (HHcy) is considered to increase the risk of sarcopenia (S) and remains controversial. In this study, we aimed to investigate the prevalence of S among older Chinese adults and explore whether homocysteine (Hcy) was independently associated with S.MethodsThis cross-sectional study was performed among older adults hospitalized in the Geriatric Hospital of Nanjing Medical University between June 2017 and December 2021. We measured all participants' serum Hcy levels, hand grip strength, gait speed and appendicular skeletal muscle index(ASMI) using bioelectrical impedance analysis (BIA). S was defined based on the criteria of the Asian Working Group for Sarcopenia 2 (AWGS2), which included muscle mass (ASMI< 7.0 kg/m2 for men and ASMI< 5.7 kg/m2 for women by BIA) and low muscle strength (handgrip strength < 28 kg for men and < 18 kg for women), and/or gait speed < 1.0 m/s. HHcy defined as Hcy ≥10 μmol/L. The strength of the association between Hcy and the risk of S was analyzed by multivariate logistic regression using three models that adjusted for possible confounding variables to calculate the odds ratios (ORs) and 95% confidence intervals (CIs).ResultsAmong the 441 subjects, 161 (36.5%) were diagnosed with S, and 343 (77.8%) were diagnosed with HHcy. A significant association was detected between S and serum Hcy per 1-μmol/L increase after adjustment for age, gender, education, smoking, body mass index (BMI), Mini Nutritional Assessment Short Form (MNA-SF), alanine aminotransferase (ALT), C-reactive protein (CRP), hemoglobin (Hb), albumin (ALB), diabetes, kidney disease, and statin use (OR = 1.07, 95% CI = 1.03-1.12, P = 0.002). The OR for S in the HHcy group (≥10 μmol/L) was nearly 5-fold that in the normal Hcy group (OR 4.96, 95% CI 2.67-9.24, P < 0.001). In a gender-based subgroup analysis that adjusted for age, education, smoking, BMI, MNA-SF, ALT, CRP, Hb, and ALB, female subjects with HHcy had an increased risk of S (OR 10.35, 95% CI 2.84-37.68, P < 0.001).ConclusionsOur results demonstrated that elevated Hcy levels have an independent association with S in older adults. This suggests that the downward adjustment of HHcy (cutoff value < 10 μmol/l) might decrease the risk of S.

Project description:BackgroundFrailty is common and not limited to older age group. Serum α-Klotho works as a biomarker of anti-aging effect. However, there is limited research about the relationship between them in middle-aged and older people and controversy still exists.MethodsBased on data from National Health and Nutrition Examination Survey (NHANES) 2007-2016, we constructed weighted logistic regression models and conducted sensitivity tests to investigate the correlation between frailty and α-Klotho among people aged 40 to 79. And then their relationship was visualized by Restricted Cubic Spline (RCS). Finally, the stratified analyses and interaction tests of covariables was presented in the forest plot.ResultsA total of 7052 individuals were involved in this study, with mean age of 62.76 ± 0.18 years and females accounting for 51.05%. 2554 of them were in "frailty". After adjustment for relevant covariables, weighted logistic regression models showed that the odds ratio and 95% confidence interval [ORs (95%CI)] of correlation between frailty and Natural Logarithm(ln)-transformed α- Klotho[ln(α-Klotho)] was 0.63 (0.50, 0.79); we then performed a sensitivity analysis and found that the results remained stable. In model 3, individuals in quartiles 2, 3, and 4 showed statistical differences compared with the lowest ln(α-Klotho) quartiles, ORs (95% CI) were 0.74 (0.59, 0.93), 0.72 (0.57, 0.91), 0.71 (0.57, 0.87), respectively. Subsequently, non-linear associations were exhibited by RCS (p<0.001). The turning point for α-Klotho and ln(α-Klotho) were 785.7(pg/ml) and 6.67, respectively. Finally, analysis of the relationship between different levels of ln(α-Klotho) and frailty in different populations revealed differences between groups. The results of the interaction test showed that no other covariables had significant interaction with serum α-Klotho in our study.ConclusionThe L-shaped and negative correlation was found between α-Klotho and frailty among people aged 40 to 79 in the NHANES from 2007 to 2016.

Dataset Information

Klotho locus, metabolic traits, and serum hemoglobin in hospitalized older patients: a genetic association analysis.

Publications

Klotho locus, metabolic traits, and serum hemoglobin in hospitalized older patients: a genetic association analysis.

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