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Klotho Levels and Their Relationship with Inflammation and Survival among Alcoholic Patients.

ABSTRACT: α-Klotho (Klotho) is an antiaging hormone with anti-inflammatory and antioxidative properties. Some studies suggest that Klotho increases in response to enhanced oxidative damage and inflammation. Alcoholism is a proinflammatory condition. The aim of this study was to analyze the relationship between Klotho and the serum levels of the inflammatory markers in alcoholic liver disease and to assess its prognostic value. We included 184 alcoholics and 35 age- and sex-matched controls. We determined the serum levels of Klotho, the tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, and malondialdehyde (MDA), and routine laboratory variables. Patients were followed-up with during 16 ± 18 months; 67 patients died. Klotho levels were higher among cirrhotics (with KW = 37.00 and p < 0.001) and were related to the Child-Pugh score (with KW = 15.96 and p < 0.001) and to the TNF-α (ρ = 0.28; p < 0.001) and MDA (ρ = 0.21; p = 0.006). The child's groups were associated with mortality, both in the univariate (with the log-rank = 13.56, p = 0.001, Breslow = 12.33, and p = 0.002) and multivariate (with β = 0.43, p = 0.02, and OR = 1.53 (1.07-2.15)) analyses, also introducing Klotho and the TNF-α as dichotomic variables. However, the independent prognostic value of the Child's groups was displaced by Klotho when only cirrhotics were considered; Klotho, over the median (574.4 pg/mL), was associated with higher mortality (with p = 0.04 and OR = 2.68 (1.06-6.84)). We conclude that Klotho is increased in liver cirrhosis. It is directly related to TNF-α, MDA, and to mortality in cirrhotics.

SUBMITTER: Martin-Gonzalez C

PROVIDER: S-EPMC9405938 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Klotho Levels and Their Relationship with Inflammation and Survival among Alcoholic Patients.

Martín-González Candelaria C Espelosín-Ortega Elisa E Abreu-González Pedro P Fernández-Rodríguez Camino C Vera-Delgado Víctor Eugenio VE González-Navarrete Lourdes L García-Rodríguez Alen A Riera Antonio Martínez AM González-Reimers Emilio E

Biomolecules 20220820 8

α-Klotho (Klotho) is an antiaging hormone with anti-inflammatory and antioxidative properties. Some studies suggest that Klotho increases in response to enhanced oxidative damage and inflammation. Alcoholism is a proinflammatory condition. The aim of this study was to analyze the relationship between Klotho and the serum levels of the inflammatory markers in alcoholic liver disease and to assess its prognostic value. We included 184 alcoholics and 35 age- and sex-matched controls. We determined ...[more]

PMID: 36009045

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Project description:BackgroundKlotho, an anti-aging protein, is linked to energy metabolism. There is limited research on the association of serum klotho and triglyceride glucose (TyG) index-related indicators. Our research aims to investigate the relationship of serum klotho with TyG-BMI (body mass index), TyG-WC (waist circumference), and TyG-WHtR (waist-to-height ratio).MethodsFrom 2007 to 2016, we examined 6,370 participants in the National Health and Nutrition Examination Survey (NHANES). The enzyme-linked immunosorbent assay (ELISA) was utilized to measure serum klotho. We calculated the TyG-BMI, TyG-WC, and TyG-WHtR based on fasting triglycerides, fasting glucose, BMI, WC, and WHtR. Multiple linear regression analysis was used to evaluate the association of serum klotho with TyG-BMI, TyG-WC, and TyG-WHtR. Additionally, generalized additive model (GAM) and smoothing curves were used to evaluate the linear and nonlinear relationships. A piecewise regression model was also utilized to test for threshold effects and determine the breakpoints. Finally, the potential independent associations of serum klotho with TyG-BMI, TyG-WC, and TyG-WHtR were further explored using subgroup analysis.ResultsWe observed a statistically significant difference in serum klotho levels across different quartiles of the population. Based on the multiple linear regression analysis, serum klotho levels were negatively associated with TyG-related indicators. There was a nonlinear relationship between the serum klotho and TyG-BMI, TyG-WC, and TyG-WHtR. The segmented regression analysis revealed that the breakpoints of TyG-BMI, TyG-WC, and TyG-WHtR were 5.42, 6.67, and 1.89, respectively. Subgroup analysis showed that TyG-related indicators interacted with gender and diabetes.ConclusionsIn this study, a negative and nonlinear relationship was identified between serum klotho and TyG-related indicators. Further research is needed to clarify the potential mechanisms that may link serum klotho to TyG-BMI, TyG-WC, and TyG-WHtR.

Project description:Background: Recent literature suggests that α-Klotho, a widely recognized anti-aging protein, is involved in longevity as well as in many diseases, including Alzheimer's disease, and depression. Although the Klotho gene encodes α-Klotho, a single transmembrane protein with intracellular and extracellular domains, the relationship between Klotho gene polymorphism and circulating α-Klotho levels in patients with major depressive disorder (MDD) is not clear. Methods: A total of 144 MDD patients and 112 age-matched healthy controls were included in this study. The Klotho genetic polymorphisms (rs9536314, rs9527025, and rs9315202) and plasma α-Klotho levels were measured by PCR and ELISA, respectively. The severity of depressive symptoms was estimated using the Hamilton Depression Scale (HAMD). Results: We found a significantly lower level of plasma α-Klotho in the MDD patients than in controls. Among them, only elderly MDD patients (first episode) showed significantly lower α-Klotho levels than the age-matched controls, while elderly recurrent and young MDD patients showed no difference in plasma α-Klotho levels from age-matched controls. The young MDD group showed a significantly earlier onset age, higher plasma α-Klotho levels, and lower HAMD scores than those in the elderly MDD group. While the plasma α-Klotho levels were higher in rs9315202 T alleles carrier regardless age or sex, the rs9315202 T allele was negatively correlated with disease severity only in the elderly MDD patients. Conclusion: The results of our study showed that only elderly MDD patients showed a decrease in plasma α-Klotho levels along with an increase in disease severity as well as an association with the number of rs9315202 T alleles, and not young MDD patients compared to age-matched controls. Our data suggest that circulating α-Klotho levels combined with Klotho genetic polymorphisms are important in elderly MDD patients, particularly carriers of the Klotho gene rs9315202 T allele.

Dataset Information

Klotho Levels and Their Relationship with Inflammation and Survival among Alcoholic Patients.

Publications

Klotho Levels and Their Relationship with Inflammation and Survival among Alcoholic Patients.

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