Abstract
Based on the fact that klothoβdeficient 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 65.9βΒ±β8.2; range 40β92 years) and 71 men (mean age 65.7βΒ±β9.1; range 30β82 years). The control population consisted of 383 subjects; 231 women (mean age 65.8βΒ±β8.4; range 35β90 years) and 152 men (mean age 61.5βΒ±β9.3; range 28β87 years). Four SNPsβG395A in the promoter region, G1110C in exon 2, C1818T and C2298T in exon 4βwere genotyped. A significant genotypic and allelic association was observed in SNP C2998T and knee OA, while genotype GA of SNP G395A was significantly associated (pβ=β0.039) 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. Β© 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:1466β1470, 2008