VITAMIN-D-RECEPTOR GENOTYPE IS ASSOCIATED WITH RADIOGRAPHIC OSTEOARTHRITIS AT THE KNEE

Osteoporosis and osteoarthritis are age-related disorders of the skele ton with genetic components. Low bone density is a risk factor for ost eoporotic fracture while osteoarthritis is associated with increased b one density, The 1,25-dihydroxyvitamin D-3 receptor (VDR) gene locus w as previously found to be associated with bone density, We therefore s tudied the relationship between radiographic osteoarthritis at the kne e and VDR genotype in a population-based sample (n = 846), using molec ular haplotyping of anonymous intragenic DNA polymorphisms, Radiograph ic osteoarthritis was defined using the Kellgren score, which is based on the assessment of osteophytes and joint space narrowing (JSN), We show that one VDR haplotype allele is significantly overrepresented in individuals with knee osteoarthritis and associated with a 2.27-fold increased relative risk (95% confidence interval 1.46, 3.52). Adjustme nt for bone density at the femoral neck did not change these results, indicating that the association is not mediated by bone density, The a ssociation appeared to be largely explained by the presence of osteoph ytes rather than JSN, Our results indicate a role of the VDR gene in t he pathogenesis of osteophytes while linkage disequilibrium with anoth er nearby gene, i.e., the collagen type IIa1 gene encoding the most ab undant protein in cartilage, might contribute to the association.