Adjacent genes, for COL2A1 and the vitamin D receptor are associated with separate features of radiographic osteoarthritis of the knee

Objective, To study the association of the COL2A1 genotype, in relation to the vitamin D receptor (VDR) genotype, with features of radiographic osteoa rthritis (ROA) in a population of elderly men and women. Methods. In this cross-sectional study, we analyzed a population-based samp le of 851 men and women ages 55-80 years from a large cohort study, the Rot terdam Study. We determined the prevalence of ROA of the knee according to the Kellgren/Lawrence (K/L) score and features of ROA (presence of osteophy tes and narrowing of the joint space [JSN]) without considering clinical pa rameters of the disease. Genotypes were determined at a variable-number tan dem repeats marker 1 kb downstream of the COL2A1 gene using a newly develop ed heteroduplexing method. The VDR genotype was previously determined by a direct molecular haplotyping polymerase chain reaction method to establish the phase of alleles at 3 adjacent restriction fragment length polymorphism s for Bsm I, Apa I, and Taq I. Results. We found the COL2A1 genotype to be associated with a 2-fold increa sed risk for JSN, but not with osteophytes or the K/L score. We had previou sly found the VDR genotype to be associated with osteophytes and the K/L sc ore, but not with JSN, When the COL2A1 genotype was analyzed in combination with the VDR genotype, we found evidence suggesting that the presence of h aplotypes of the 2 genes was associated with increased risk for ROA, Conclusion, Our findings demonstrate that both the COL2A1 gene and the VDR gene are involved in ROA, but in separate features. The COL2A1 genotype is associated with JSN, while the VDR genotype is associated with osteophytes.