Klotho in chronic kidney disease in Indian population

Introduction: Klotho, an anti-aging protein primarily expressed in the kidney is the suppressor of the expression of multiple aging phenotypes. Aims and Objectives: Present study aimed at analyzing the soluble alpha-Klotho levels in serum, prevalence of its KL-VS (F352V) and promoter (G-395A) polymorphisms in chronic kidney disease (CKD) patients & controls and their influence on soluble alpha-Klotho levels. Materials and Methods: CKD (N=100) and healthy Controls (N=97) were enrolled for the study. Soluble alpha-Klotho levels were analysed by ELISA at recruitment of subjects and further in CKD stage 1 & 2 (N=10), stage 3 & 4 (N= 14) and stage 5 (N=48) at 6 month. Genotyping of T42568G SNP (rs 9536314, F352V, of the KL-VS variant) and G-395A SNP (rs1207568) of the promoter polymorphism of Klotho gene was carried out by Taqman genotyping assay using Real Time PCR. The influence of the genotypes on alpha-Klotho levels was also examined. Results: As compared to the controls, there was a significant decrease in alpha -Klotho levels in CKD stage 1 & 2 (42.1%, p=0.01), stage 3 & 4 (74.2%, p=0.001) and in stage 5 (78.2%, p=0.001) in serum. However no significant change was seen in alpha-Klotho levels in patients at six months as compared to the levels at recruitment. The prevalence of heterozygous and homozygous genotypes for both these SNPs was low as compared to wild type genotype. The distribution of genotypes did not show any significant difference between CKD and Control groups and alpha-Klotho levels were not influenced by genotypes of both the polymorphisms. Conclusion: Soluble alpha-Klotho levels were found to decrease significantly at initial CKD stages. Thus, analysis of soluble alpha-Klotho levels may help in identifying CKD patients much before the severity sets in.