Haplotype analysis of three polymorphisms of the COL2A1 gene and associations with generalised radiological osteoarthritis

It was investigated whether radiographic osteoarthritis (ROA) is associated with specific haplotypes of the COL2A1 gene. Radiographs of knees, hips, h ands, and spine were scored for the presence of ROA in subjects of 55-70 Se ars from a population-based cohort study, the Rotterdam study. Cases had RO A in 3 or more joint groups; controls, from the same population, had ROA in less than 3 joint groups. Allele frequencies of 3 dimorphisms (HaeIII, Hin dIII, MaeII) and a VNTR polymorphism of the COL2A1 gene were determined. Th e VNTR allele 14R2 and the HindIII polymorphism showed a significant associ ation. Haplotype analysis of the HaeIII, HindIII and VNTR polymorphisms sho wed that a specific haplotype (1-2-14R2) is strongly associated with ROA in 3 or more joint groups (OR = 5.3, 95 % CI 2.3-12.7). Our results suggest t hat a specific haplotype of the COL2A1 locus may predispose to generalised ROA.