Haplotypes of the low-density lipoprotein receptor-related protein 5 ( LRP5) gene: Are they a risk factor in osteoarthritis?

Several genome-wide scans have revealed an osteoarthritis (OA)-susceptibility locus on chromosome 11q in close proximity to the low-density lipoprotein receptor-related protein 5 ( LRP5) gene. The regulation of bone mass is under the control of LRP5 and since increased bone mass is thought to play a role in the pathology of OA we examined LRP5 polymorphisms and haplotypes to determine if variants of this locus may predispose to OA. A UK control population of 187 individuals was examined for five commonly occurring polymorphisms against a cohort of 158 DNAs from patients with knee OA. An additional UK cohort was also examined to confirm the findings of the first study; this second group consisted of 110 knee OA patients. Haplotype analysis was also performed on patient and control DNAs. A study of individual polymorphisms revealed no association with disease. However, haplotype analysis of the initial two populations revealed a common haplotype (C-G-C-C-A) that provided a 1.6-fold increased risk of OA ( P c = 0.021). The data obtained from the second cohort confirmed the initial findings, with a 1.6-fold increased risk observed within this cohort for the risk haplotype ( P = 0.012). A closer investigation of LRP5 and associated Wnt signalling molecules in OA will help determine disease aetiology and the development of novel treatment strategies that specifically target the bone compartment.