When the genotype data were used to construct haplotypes, the VDR AaTt joint genotype appeared to pose a remarkably lower odds (OR = 0.26, 95% CI = 0.08-0.91) of osteophyte compared with the AAtt joint genotype.
The strongest associations observed (statistically significant after correcting for multiple comparisons) were between COX2 and change in osteophyte grade (P < 0.001) and Kellgren-Lawrence grade (P < 2 x 10(-5)), and between the genes for vitamin D receptor (P < 0.002) and a thrombospondin (THSD2) (P < 0.002) and change in osteophyte grade.
Allelic variation in the vitamin D receptor gene was associated with severity of osteophytosis (adjusted OR "TT" v "tt" 0.41, 95% CI 0.17, 0.97), presence of disc narrowing (adjusted OR "TT" v "tt" 0.45, 95% CI 0.20, 0.99) and weakly with presence of osteophytosis (adjusted OR "TT" v "tt" 0.47, 95% CI 0.19, 1.16) but not with severity of disc narrowing (OR "TT" v "tt" 1.05, 95% CI 0.40, 2.72) or apophyseal arthritis (OR "TT" v "tt" 0.63, 95% CI 0.24, 1.59).
Our results indicate a role of the VDR gene in the pathogenesis of osteophytes while linkage disequilibrium with another nearby gene, i.e., the collagen type IIa1 gene encoding the most abundant protein in cartilage, might contribute to the association.