Association of KLOTHO gene polymorphisms with knee osteoarthritis in Greek population

Abstract

Based on the fact that klotho-deficient mice exhibit multiple aging phenotypes, including osteopenia and subchondral sclerosis of joints and on the recent observation that KLOTHO gene plays an important role in calcium/phosphate homeostasis, we explored the possibility whether human KLOTHO gene polymorphisms are associated with osteoarthritis (OA). A total of 752 individuals participated in the study. The knee OA group consisted of 369 patients; 298 women (mean age 65.9 AE 8.2; range 40-92 years) and 71 men (mean age 65.7 AE 9.1; range 30-82 years). The control population consisted of 383 subjects; 231 women (mean age 65.8 AE 8.4; range 35-90 years) and 152 men (mean age 61.5 AE 9.3; range 28-87 years). Four SNPs-G395A in the promoter region, G1110C in exon 2, C1818T and C2298T in exon 4-were genotyped. A significant genotypic and allelic association was observed in SNP C2998T and knee OA, while genotype GA of SNP G395A was significantly associated (p ¼ 0.039) with knee OA in females only. For the first time, an association was observed between SNPs G395A and C2998T of the KLOTHO gene and knee osteoarthritis implicating KLOTHO in OA pathogenesis. ß

Klotho regulates postnatal neurogenesis and protects against age-related spatial memory loss

“…This could be an effect of the model as OE mice overexpress only ~1.5x normal KL (Kurosu et al 2005). However, the cognitive enhancing human polymorphism, KL-VS, also arises with mild serum KL elevation (Dubal et al 2014) and minor polymorphic KL changes correlate with human disease risk (Arking et al 2002; Kawano et al 2002; Arking et al 2005; Deary et al 2005; Tsezou et al 2008). As such, mild KL increase or decrease may be sufficient to affect brain function especially with increasing age.…”

<i>KLOTHO</i> Gene Polymorphisms G-395A and C1818T Are Associated with Low-Density Lipoprotein Cholesterol and Uric Acid in Japanese Hemodialysis Patients

“…There were no significant differences in allele frequencies of G-395A and those of the C1818T between HD patients and healthy subjects. Kawano et al[ 10] reported that the allele frequency for the A allele in G-395A was 0.128 and for the T allele in C1818T it was 0.248 in Japanese healthy women over 65 years. Our results on allele frequency are almost consistent with the previous literature.…”

“…A map of KLOTHO is shown in figure 1. One SNP located in the promoter region (G-395A) has been reported to be associated with bone mineral density [8, 9], osteoarthritis [10], systolic blood pressure [11], atherosclerotic coronary artery disease [12, 13], and cardioembolic stroke [14]. Another SNP located in exon 4 (C1818T) has been reported to be associated with bone mineral density [8], fasting glucose [11], and atherosclerotic coronary artery disease [13].…”

Lack of functional KL-VS polymorphism of the KLOTHO gene in the Korean population

“…, 2014). The KL-VS variant spans exon 2 and its flanking sequence, and is common in Caucasians (Low et al , 2005; Freathy et al , 2006; Riancho et al , 2007; Novelli et al , 2008; Tsezou et al , 2008; Invidia et al , 2010; Nzietchueng et al , 2011; Tavakkoly-Bazzaz et al , 2011). KL-VS can influence KLOTHO gene expression in vitro, and it has been inconsistently associated with human longevity in European and American populations (Majumdar et al, 2010).…”