Association of KLOTHO gene polymorphisms with knee osteoarthritis in Greek population

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 ± 8.2; range 40–92 years) and 71 men (mean age 65.7 ± 9.1; range 30–82 years). The control population consisted of 383 subjects; 231 women (mean age 65.8 ± 8.4; range 35–90 years) and 152 men (mean age 61.5 ± 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 = 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.