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Rheumatology 2000; 39: 299-306
© 2000 British Society for Rheumatology

Linkage analysis of candidate genes as susceptibility loci for osteoarthritis—suggestive linkage of COL9A1 to female hip osteoarthritis

Z. Mustafa, K. Chapman, C. Irven, A. J. Carr1, K. Clipsham1, J. Chitnavis1, J. S. Sinsheimer2, V. A. Bloomfield1, M. McCartney3, O. Cox1, B. Sykes and J. Loughlin

University of Oxford, Institute of Molecular Medicine, Oxford,
1 Nuffield Orthopaedic Centre, Oxford, UK,
2 Departments of Biomathematics and Biostatistics, University of California, Los Angeles, USA and
3 Musgrave Park Hospital, Belfast, UK

Objective. To examine 11 candidate genes as susceptibility loci for osteoarthritis (OA).

Methods. A total of 481 families have been ascertained in which at least two siblings have had joint replacement surgery of the hip, or knee, or hip and knee for idiopathic OA. Each candidate gene was targeted using one or more intragenic or closely linked microsatellite marker. The linkage data were analysed unstratified and following stratification by sex and by joint replaced (hip or knee).

Results. The analyses revealed suggestive linkage of the type IX collagen gene COL9A1 (6q12-q13) to a subset of 132 families that contained affected females who were concordant for hip OA (female-hip) with a P-value of 0.00053 and logarithm of the odds (LOD) score of 2.33 [corrected P-value of 0.0016, corrected LOD score of 1.85].

Conclusions.COL9A1 may therefore be a susceptibility locus for female hip OA. In addition, there was weak evidence of linkage to HLA/COL11A2 (6p21.3) in female hip OA with a corrected P-value of 0.016.

KEY WORDS: Osteoarthritis, Linkage, Affected sibling pairs, COL9A1.

Correspondence to: J. Loughlin.


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