Involvement of Single Nucleotide Variants in the Klotho Gene Among Obesity Individuals with and without Type 2 Diabetes Mellitus in the Saudi Population

Arwa A Alageel,1 Imran Ali Khan2 1Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia; 2Medical Genomic Research Department, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard-Health Affairs, Riyadh, Saudi ArabiaCorrespondence: Imran Ali Khan, Email [email protected]: Aging is characterized by the gradual physiological changes and alterations that accumulate over time in the human body. The combination of obesity and ageing can lead to an increased risk of serious health issues or death. Single nucleotide variants (SNVs) in the Klotho gene were commonly studied, including that in type 2 diabetes mellitus (T2DM).Aim: The aim of this study is to examine the possible effect of SNVs in Klotho on the obese population in Saudi Arabia using middle-aged participants with and without T2DM.Methods: This study consists of 100 controls and 100 obesity patients, in which 50 had T2DM and the remaining 50 were obese without T2DM. Genotyping was performed with PCR, and Sanger sequencing analysis was used to validate the molecular association.Results: In this study, rs1207568 (p = 0.001– 0.003) and rs9527025 (p = 0.001– 0.00004) SNVs were associated with obesity cases. However, none of the genotypes or allele frequencies showed a positive association with the rs564481 SNV (p = 0.344– 0.881). The multiple linear regression model showed that waist and hip were associated (p = 0.01– 0.02). ANOVA analysis showed age (p = 0.04), hip (p = 0.002), SBP, and TC (p = 0.02) were associated. Finally, SNV (rs1207568 and rs95270250) and obesity (p < 0.001) associations were confirmed through gene multifactor dimensionality reduction analysis with gene–gene interaction, dendrogram, and graphical depletion method.Conclusion: This study concludes that rs1207568 and rs9527025 SNVs are associated with obesity in the Saudi population. Additional genetical statistics showed significant association between dependent and independent variables. SNVs in Klotho play a role in the Saudi population’s susceptibility to obesity.Keywords: Klotho gene, obesity, type 2 diabetes mellitus, rs1207568/G395A, rs564481 /C1818T, rs9527025/C370S