Association of Klotho Gene Polymorphisms with Type 2 Diabetes Mellitus

Pakistan Journal of Health Sciences, Journal Year: 2025, Volume and Issue: unknown, P. 295 - 301

Published: Jan. 31, 2025

Genetic variants in the Klotho gene could influence way β-cells function and effectively glucose functions, this might development of Type 2 Diabetes Mellitus. Objectives: To investigate association between polymorphisms rs677332 to determine risk developing type II diabetes a case-control study. Methods: This study was conducted from Feb 2024 July at Department Pathology, Rashid Latif Medical College, Lahore. The total number participants n=586, sample n=293 case diabetics 293 controls. DNA extracted blood samples genotyped using Polymerase Chain Reaction followed by restriction digestion validated through Sanger sequencing. evaluate genetic clinical data, statistical tests were performed with SPSS version 25.0 PLINK (v1.07). Logistic regression analysis, adjusted for age, sex, region, used associations Fasting levels as reference variable multiple nominal regression. Results: SNPs polymorphism significantly correlated, underscoring importance BMI, heredity risk. confirmed that individuals AA genotype linked 73% rise likelihood (OR=1.73, p=0.004). Conclusions: may serve potential protective factor against outcomes report significance metabolic health indicate possible advantages screening early treatment

Language: Английский

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Influence of Klotho Protein Levels in Obesity and Sarcopenia: A Systematic Review

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 1915 - 1915

Published: Feb. 23, 2025

The Klotho gene is recognized for its anti-aging properties. Its downregulation leads to aging-like phenotypes, whereas overexpression can extend lifespan. protein exists in three forms: α-klotho, β-klotho and γ-klotho. α-klotho has two isoforms: a membrane-bound form, primarily the kidney brain, secreted klotho present blood, urine, cerebrospinal fluid. functions as co-receptor fibroblast growth factor-23 (FGF23), regulating phosphate metabolism. form controls various ion channels receptors, while regulates endocrine FGFs, including FGF19 FGF21. interaction between FGF21 muscle critical development of sarcopenic obesity. This systematic review, registered PROSPERO conducted following PRISMA guidelines, evaluates levels individuals with obesity or study includes overweight, obese, obese adults compared those normal body mass index. After reviewing 713 articles, 20 studies were selected, observational, cross-sectional, cohort studies, clinical trials. Significant associations obesity, metabolic syndrome (MS), cardiovascular risk observed. Exercise dietary interventions positively influenced levels, which linked improved strength slower decline. potential biomarker MS, Further research needed explore mechanisms therapeutic potential.

Language: Английский

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Association of serum Klotho concentrations with abdominal obesity among middle-aged adults in the US: evidence from NHANES 2011-2016

Nutrition, Journal Year: 2025, Volume and Issue: 136, P. 112809 - 112809

Published: April 17, 2025

The role of Klotho in metabolic processes and aging-related conditions is well-established. However, the link between visceral adipose tissue (VAT) remains understudied. aim this study was to explore relationship levels both VAT area abdominal obesity. A cross-sectional analysis encompassing 3316 middle-aged individuals conducted using data from National Health Nutrition Examination Survey (NHANES 2011 2016). Dual-energy X-ray absorptiometry (DXA) utilized assess region, while obesity defined by a exceeding 100 cm². evaluated multiple linear regression, association assessed multivariate logistic regression. To linearity dose-response curve, restricted cubic splines were applied. Higher associated with lower (β -5.57, 95% CI = -9.83 - -1.30; P 0.011) reduced incidence (OR 0.57, 0.42-0.78; < 0.001), after adjusting for all model variables. Furthermore, smooth revealed nonlinear, L-shaped significant negative observed, curves leveling off as increased beyond 1.155 ng/mL. An nonlinear indicated saturation effect. These findings warrant attention suggest that further investigation into serum necessary.

Language: Английский

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Anti-aging protein α-Klotho is potential for reducing comorbidity risk of cardiometabolic diseases in vulnerable populations and enhancing long-term prognosis

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: May 14, 2025

Language: Английский

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Sex-specific association between serum α-klotho levels and sleep disturbances in the elderly: a cross-sectional study

European journal of medical research, Journal Year: 2025, Volume and Issue: 30(1)

Published: May 20, 2025

Sleep disturbances (SD) exhibit a high prevalence among older adults and exert considerable influence on cardiovascular health, quality of life, other facets well-being. α-Klotho, an anti-aging factor that diminishes with advancing age, has been implicated in multitude age-related conditions. However, the relationship between SD α-klotho levels elderly remains inadequately investigated, potential sex-specific differences this association warrant further exploration. This study utilized data from National Health Nutrition Examination Survey (NHANES) to initially investigate SD, analyses conducted separately for both sexes. In addition, was delineated using restricted cubic spline (RCS) curves. A total 5,957 participated study, revealing at 29.5%. Notably, females exhibited higher compared men (33.6% vs. 25.3% males). After adjusting covariates, were hypothesized be associated decreased incidence SD. Differences also existed sexes, as demonstrated by significant correlation serum females, but not males. Results RCS analysis indicated negative nonlinear consistent across sexes general population. The findings current revealed development population, notable differences.

Language: Английский

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Preeclampsia as a Study Model for Aging: The Klotho Gene Paradigm

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 902 - 902

Published: Jan. 22, 2025

Aging and pregnancy are often considered opposites in a woman’s biological timeline. is defined by gradual decline the functional capabilities of an organism over its lifetime, while characterized presence transient placenta, which fosters cellular fitness necessary to support fetal growth. However, context preeclampsia, aging share common hallmarks, including clinical complications, altered phenotypes, heightened oxidative stress. Furthermore, women with pregnancies complicated preeclampsia tend experience age-related disorders earlier than those healthy pregnancies. Klotho, gene discovered fortuitously 1997 researchers studying mechanisms, primarily expressed kidneys but also lesser extent several other tissues, placenta. The Klotho protein membrane-bound that, upon cleavage ADAM10/17, released into circulation as soluble (sKlotho) where it plays role modulating This review focuses on involvement sKlotho development disorders, well expression recently Mytho gene, has been associated skeletal muscle atrophy.

Language: Английский

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Relationship of sKlotho with hemoglobin level in patients undergoing maintenance hemodialysis: a case–control study

Therapeutic Advances in Chronic Disease, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 1, 2025

Background: Klotho is a kidney-derived protein that involved in various kidney diseases. The role of serum soluble (sKlotho) the anemia patients undergoing hemodialysis has not been well characterized. Objective: We aimed to characterize relationship between sKlotho and hemoglobin (Hb) levels this group patients. Design: A single-center cross-sectional study 208 maintenance (MHD) 50 healthy controls was performed June 1 31, 2023. Methods: Demographic information biomedical parameters, such as age, body mass index, medication use, their Hb, albumin, interleukin-6, concentrations, were obtained. Patients MHD allocated achieved Hb target (⩾110 g/L) did (<110 g/L). Correlation analysis multivariate logistic linear regression analyses evaluate with concentration. Results: Participants had lower concentrations than controls. Those who level given fewer erythropoiesis-stimulating agents albumin but higher interleukin-6 those target. concentration positively correlated inversely associated incidence lack achievement level. Multivariate models revealed there close association after adjustment for potential confounders (odds ratio: 0.335, 95% confidence interval: 0.142–0.791, p = 0.013). This closer on when included continuous variable. Conclusion: circulating very low, deficiency independently high risk MHD. Therefore, routine monitoring might be useful management renal

Language: Английский

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Vitamin C Inhibits Lipopolysaccharide-Induced Hyperinflammatory State of Chronic Myeloid Leukemia Cells through Purinergic Signaling and Autophagy

Nutrients, Journal Year: 2024, Volume and Issue: 16(3), P. 383 - 383

Published: Jan. 29, 2024

Background: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the overproduction of white blood cells, leading to symptoms such as fatigue, infections, and other complications. CML patients must take measures prevent infections mitigate exacerbation cancer cell proliferation comorbidities. Methods: This study investigated whether vitamin C can suppress hyperinflammatory activation K-562 cells induced lipopolysaccharide (LPS) purinergic signaling (ATP P2X7 receptor) autophagy play role in it. Two different doses (5 µg/mL 10 µg/mL) were employed, along with lysosome inhibitor chloroquine (CQ; 100 µM), administered 2 h prior LPS stimulation (10 ng/mL) for duration 22 (3 × 105 cells/mL/well). Results: Both reduced release interleukin-6 (IL-6) µg/mL, p < 0.01 0.01) tumor necrosis factor (TNF) LPS. Furthermore, + CQ-stimulated at concentration inhibited expression LC3-II (p 0.05). Conversely, both led anti-inflammatory cytokine interleukin-10 (IL-10) 0.01), while only dose Klotho 0.01). In addition, accumulation ATP decreased receptor mRNA level. Conclusions: Vitamin inhibits state primarily inhibiting accumulation, expression, signaling.

Language: Английский

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Abnormal Histopathological Expression of Klotho, Ferroptosis, and Circadian Clock Regulators in Pancreatic Ductal Adenocarcinoma: Prognostic Implications and Correlation Analyses

Biomolecules, Journal Year: 2024, Volume and Issue: 14(8), P. 947 - 947

Published: Aug. 5, 2024

Pancreatic ductal adenocarcinoma (PDAC) is an extremely lethal tumor with increasing incidence, presenting numerous clinical challenges. The histopathological examination of novel, unexplored biomarkers offers a promising avenue for research, significant translational potential improving patient outcomes. In this study, we evaluated the prognostic significance ferroptosis markers (TFRC, ALOX-5, ACSL-4, and GPX-4), circadian clock regulators (CLOCK, BMAL1, PER1, PER2), KLOTHO in retrospective cohort 41 patients deceased by PDAC. Immunohistochemical techniques (IHC) multiple statistical analyses (Kaplan-Meier curves, correlograms, multinomial linear regression models) were performed. Our findings reveal that are directly associated PDAC mortality, while inversely associated. Notably, TFRC emerged as strongest risk marker mortality (HR = 35.905), whereas CLOCK was identified most protective 0.01832). Correlation indicate positively correlated each other, regulators, which also correlate expression. contrast, exhibit inverse correlations markers. Among variables examined, only presence chronic pathologies showed association expression patterns several proteins studied. These underscore complexity pathogenesis highlight need further research into specific molecular mechanisms driving disease progression.

Language: Английский

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Association between the triglyceride–glucose index and serum soluble Klotho in middle-aged and older adults from NHANES 2007–2016

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Aug. 8, 2024

Klotho, an anti-aging protein, is believed to participate in metabolic diseases and play a potential protective role by regulating insulin sensitivity. This study aimed explore the relationship between triglyceride-glucose (TyG) index (a simple marker of resistance) serum soluble Klotho (S-Klotho) levels. The cross-sectional comprised 5237 adults aged 40-79 years who participated National Health Nutrition Examination Surveys (NHANES) 2007-2016. TyG was calculated as ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. levels S-Klotho were measured enzyme-linked immunosorbent assay. association investigated multiple linear regression models, smoothed curve fitting, segmented subgroup analyses, interaction tests. inversely associated with level after full adjustment (β = - 45.11, 95% CI (- 79.53, 10.69), P 0.011). Furthermore, we also found non-linear correlation saturation phenomenon levels, turning point 9.56. In addition, significant effect sex two (P for < 0.001), more pronounced observed females. Further studies are required mechanisms verify correlation.

Language: Английский

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