<i>KLOTHO</i> Gene Polymorphism of G395A Is Associated with Kidney Stones

Abstract

Background/Aims: KLOTHO, a type-1 transmembrane protein with glucurodinase activity, is expressed in tissues responsible for calcium homeostasis such as the kidney, parathyroid gland and the epithelium of the choroid plexus in the brain. Given the emerging evidence indicating a novel regulatory function for KLOTHO protein in renal calcium and phosphate homeostasis, the present study aims to investigate the association between KLOTHO genetic polymorphisms and kidney stone (KS). Methods:KLOTHO gene polymorphisms G395A in the promoter region, F252V in exon 2, and C1818T in exon 4 were investigated in 108 patients with renal calcium stone formation and 51 age-matched healthy volunteers with no history of renal stone formation, using polymerase chain reaction. Results: GG genotype of G395A KLOTHO polymorphism had approximately 2-fold increased KS risk compared with the homozygous genotype AA and heterozygote GA (OR 1.849, 95% CI 1.016–3.364, p = 0.044). We also found that non-A allele carriers had significantly higher KS risk associated with the KS clinical characteristics including hypercalcemia, hypophosphatemia and phosphaturia. Conclusion: Our findings suggested that the G395A polymorphism of KLOTHO gene is associated with the KSs and may act as a risk factor for the development of KS disease.

G-395A polymorphism in the promoter region of the KLOTHO gene and hypertension among elderly (90 years and older) Chinese individuals

“…In previous studies, the frequencies of the A allele in the G-395A SNP varied from 0.155 (Kim et al, 2008) to 0.171 (Rhee et al, 2006c) in Korean populations, 0.128 (Kawano et al, 2002) to 0.168 (Shimoyama et al, 2009) in Japanese populations, 0.191 in a Chinese Han population (Wang et al, 2010), and 0.227 in a Turkish population (Telci et al, 2011). Our results on the allele frequency were similar to those of studies conducted in East Asian populations, but not to that seen in the study conducted in the Turkish population.…”

“…The identification of SNPs in the human KLOTHO gene is currently one of the most active areas of research. So far, more than 10 SNPs have been identified in the human KLOTHO gene, and linked to fasting glucose (Rhee et al, 2006b), coronary artery disease (Imamura et al, 2006;Rhee et al, 2006a), stroke (Kim et al, 2006), bone mineral density (Kawano et al, 2002), and kidney stone (Telci et al, 2011).…”

Vitamin D Status in Patients with Recurrent Kidney Stones

“…Reduced bone mass and high risk for osteoporotic fractures as a consequence of PTH and vitamin D abnormalities have also been documented in calcium stone formers [12,13,14,15], as well as a contributing role of FGF-23 and KLOTHO gene polymorphism in the pathogenesis of calcium nephrolithiasis [16,17]. Therefore, FGF-23 and KLOTHO are likely to influence the vitamin D status in this patient population.…”

Induction of Oxidative Stress in Kidney

“…Recent studies showed that antiaging gen, klotho, is important in renal aging and OS-induced renal damage. The klotho gene encodes the klotho protein, a single transmembrane protein of the beta-glycosidase family [31]. Mice overexpressing klotho exhibit an extension in lifespan and resistance to oxidative injury.…”