Association between KLOTHO gene and hand osteoarthritis in a female Caucasian population

F Zhang, G Zhai, B S Kato, D J Hart, D Hunter, T D Spector, K R Ahmadi

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44 Citations (Scopus)


Objective: Osteoarthritis (OA) is a common complex disease with strong heritable components. In this study, we investigated the association between four putatively functional genetic variants in KLOTHO gene, a strong ageing-related gene, and hand CA in a large female Caucasian population. Methods: Subjects (n = 1015, age range 33-74 years) were selected from the TwinsUK Registry. Radiographs of both hands were taken for each individual with standard posteroanterior view. The presence/absence of radiographic OA, osteophyte and joint space narrowing (JSN) was assessed using a standard atlas. Four putatively functional single nucleotide polymorphisms (SNPs) in KLOTHO gene were genotyped using allelic discrimination assay. Association was initially estimated using Pearson's chi(2) or Fisher's exact test at allelic and genotypic levels. The direction and magnitude of significant association were further investigated by robust logistic regression with age as a. covariate. Results: We found significant association between SNP G-395A and the presence/absence of radiographic hand CA and osteophyte, but not JSN. Allele G significantly increased the risk for radiographic hand CA and osteophytes with odds ratios (ORs) of 1.44 (P = 0.008, 95% confidence interval (CI) 1.09-1.91) and 1.36 (P = 0.006, 95% CI 1.09-1.70), respectively. From logistic regression modelling, genotype GG showed more than three-fold increased risk for both radiographic hand CA (OR = 3.10, 95% CI 1.10-8.76) and osteophyte (OR = 3.10, 95% Cl 1.10-8.75) when compared to genotype AA. After adjustment for age, ORs for genotype GG further increased to 4.39 (P= 0.006, 95% Cl 1.51-12.74) for radiographic hand CA and to 4.47 (P= 0.005, 95% Cl 1.56-12.77) for osteophytes. Conclusions: Our results suggest that one variant in KLOTHO gene is associated with the susceptibility of hand OA and appears to act through osteophyte formation rather than cartilage damage. (c) 2006 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved
Original languageEnglish
Pages (from-to)624 - 629
Number of pages6
JournalOsteoarthritis and Cartilage
Issue number6
Publication statusPublished - Jun 2007


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