Evidence for a role of the genomic region of the gene encoding for the α1 chain of type IX collagen (COL9A1) in hip osteoarthritis -: A population-based study

Objective. Type IX collagen proteoglycan is an important protein in collagen networks and has been implicated in hip osteoarthritis (OA). We studied 2 COL9A1 markers (509-8B2 and 509-12B1) in relation to radiographic OA, within the framework of the Rotterdam Study, a population-based study of 7,983 subjects ages 55 years and older. Methods. We used 2 different designs, as follows: 1) a linkage study of 83 probands with multiple joints affected with radiographic OA and their 221 siblings, yielding 445 sibpairs who participated in the study, and 2) an association study in a series of 71 patients with radiographic hip OA and 269 controls without radiographic OA. All subjects were characterized for the 2 COL9A1 markers, 509-8132 and 509-12B1. The mean test was used to assess the proportion of alleles shared in concordantly affected and unaffected sibpairs. The chi-square test was used to compare the allele distributions in patients and controls. Results. Affected sibpairs with radiographic hip OA shared alleles identical by descent at markers 8132 and 12B1 significantly more often than expected (mean +/- SD 0.66 +/- 0.07 and 0.65 +/- 0.08, respectively; P < 0.05). No excess sharing for radiographic OA was observed at other joint sites. When comparing the frequency of marker 8132 and 12B1 alleles in subjects with radiographic OA and controls, the frequency of 8132 alleles in subjects with radiographic OA differed significantly(P = 0.01) from that in controls. Conclusion. Our data suggest that susceptibility for hip OA is conferred within or close to the COL9A1 gene in linkage disequilibrium with the COL9A1 509-81B2 marker.