Klotho and vitamin D in multiple sclerosis: an Italian study

Abstract

Introduction: Low vitamin D levels have been recognised as an important risk factor for autoimmune diseases, including multiple sclerosis (MS). MS is a multifactorial disease, the pathogenesis of which contributes both to genetic and environmental factors. Polymorphisms in genes codifying molecules involved in vitamin D homeostasis have been associated with hypovitaminosis D. However, the influence of polymorphisms of Klotho, which codify a protein with a pivotal role in vitamin D metabolism, have never been investigated. The aim of this study was to evaluate the association among genetic variants of Klotho, namely rs1207568 and rs9536314, serum 25(OH)D 3 levels, and multiple sclerosis (both risk and disease progression). Material and methods: 107 patients with MS and 133 healthy controls were enrolled in this study. Serum 25(OH)D 3 levels and genotyping of Klotho SNPs were evaluated in all participants by high-performance liquid chromatography and real-time polymerase chain reaction, respectively. Results: Allelic and genotypic frequencies did not differ between patients and controls. Concerning rs1207568, we found a trend toward lower serum 25(OH)D 3 levels in MS patients with A allele (mutant), both in heterozygosis (AG) and in homozygosis (AA), in comparison to MS patients with G allele in homozygosis (GG) (AG + AA 20.5 ±6.3 μg/l; GG 22.5 ±7.5 μg/l, p = 0.07). Conclusions: Our findings did not identify a role of Klotho in the genetic susceptibility to MS.

Age and Gender-related Variations of Molecular and Phenotypic Parameters in A Cohort of Sicilian Population: from Young to Centenarians

“…Insulin resistance status was assessed as homeostasis model assessment of insulin resistance (HOMA Index) according to the following formula: [insulin (μU/mL)* glycaemia (mg/dL)]/405. Vitamin D was evaluated as previously described [ 20 ].…”

Impact of Genetic Polymorphisms on the Metabolic Pathway of Vitamin D and Survival in Non-Small Cell Lung Cancer

“…The genes that encode the enzymes involved in the vitamin D pathway are highly polymorphic [27]. These genetic alterations may influence the expression of those genes in lung tumor tissue, modifying the activity of vitamin D [15,28,36,[38][39][40][41]. Therefore, they may play a vital part in the development, progression, and prognosis of NSCLC [5].…”

Klotho overexpression improves amyloid‐β clearance and cognition in the APP/PS1 mouse model of Alzheimer's disease

“…Previous studies showed that Klotho in the brain of AD patients and mouse models was significantly lower than in age‐matched healthy groups (Dubal et al, 2015; Kuang et al, 2017; Massó et al, 2015; Semba et al, 2014). More researches have provided indications that Klotho may alleviate an array of neurodegenerative diseases (Jamali‐Raeufy et al, 2017; Dubal et al, 2015; Scazzone et al, 2019; Zeldich et al, 2019). These findings provide convincing evidence that Klotho may be a novel therapeutic target for the treatment of AD.…”