The Association of Klotho Polymorphism with Disease Progression and Mortality in IgA Nephropathy

Backgrounds: IgA nephropathy (IgAN) is the most common primary glomerulonephritis causing end stage renal disease (ESRD), and vasculopathy is known to involve disease progression. Klotho, a gene related to aging, has been reported to play a role in atherosclerosis and endothelial dysfunction. We investigated whether klotho gene polymorphism affect clinical course of IgAN. Methods: The data registered for PREMIER study which enrolled the patients with biopsy proven IgAN were analyzed. Two single nucleotide polymorphisms for klotho gene, G395A of promoter region and C1818T of exon 4, were examined, and investigated the association klotho genotypes with the progression of IgAN and patient survival. Results: Clinical data from 973 patients confirmed about survival were analyzed. The allele frequency was 0.830 and 0.170 for allele G and A, and 0.816 and 0.184 for allele C and T, which were complied with Hardy-Weinberg equilibrium (p=0.996 and 0.531 respectively). Death was observed more frequently in A-allele carriers of G395A polymorphism (0.7 vs 2.6 %, GG vs GA+AA, p=0.022). Renal survival in Kaplan-Meier survival curve was also worse in same group (p=0.04). Conclusion: Klotho gene polymorphism was associated with patient survival and disease progression of IgAN.