EXTENDED REPORT

Investigation of chromosome 2q in osteoarthritis of the hand: no significant linkage in a Tasmanian population

J Stankovich¹, M M Sale¹, H M Cooley¹, M Bahlo², A Reilly¹, J L Dickinson¹, G Jones¹

¹ Menzies Centre for Population Health Research, University of Tasmania, GPO Box 252–23, Hobart, Tasmania, 7001, Australia
² The Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, 3050, Australia

Correspondence to:
Correspondence to:
Dr J Stankovich, Menzies Centre for Population Health Research, University of Tasmania, GPO Box 252–23, Hobart, Tasmania 7001, Australia;
Jim.Stankovich{at}utas.edu.au Australia

Background: Previous studies have suggested a strong genetic component to osteoarthritis (OA), especially that of the hand, and three linkage studies have suggested the existence of susceptibility loci in disparate regions of chromosome 2q.

Objective: To examine for linkage to 2q in a Tasmanian population of women and men with familial hand OA.

Methods: Hand OA (distal interphalangeal, carpometacarpal, and Heberden's nodes) was assessed by a combination of hand photographs and radiographs. A non-parametric linkage (NPL) analysis was performed on chromosome 2q of 69 members in 22 families with severe distal interphalangeal joint OA using Genehunter. A quantitative trait linkage analysis of a larger group of 456 members in 68 families was also performed using SOLAR.

Results: The maximum non-parametric linkage score was 1.05 (p=0.15) at marker IL1R1, close to the centromere. All components of hand OA scores had significant heritability in this dataset (28%–35%, all p<0.001). Despite this, the quantitative trait analysis (after adjustment for age and, where appropriate, sex) yielded maximum LOD scores of 0.90 for Heberden's nodes (both sexes combined), and 1.19 for carpometacarpal OA score (women only).

Conclusions: These results do not provide confirmation of linkage on chromosome 2q in the larger white population with hand OA. They suggest that there are regional variations in the genetic cause of hand OA and that other loci not on 2q may be important in this disease.

Keywords: osteoarthritis; linkage analysis

Abbreviations: cM, centimorgans; CMC, first carpometacarpal; DIP, distal interphalangeal; MLS, multipoint LOD score; NPL, non-parametric linkage; OA, osteoarthritis

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Greig, C, Spreckley, K, Aspinwall, R, Gillaspy, E, Grant, M, Ollier, W, John, S, Doherty, M, Wallis, G (2006). Linkage to nodal osteoarthritis: quantitative and qualitative analyses of data from a whole-genome screen identify trait-dependent susceptibility loci. Ann Rheum Dis 65: 1131-1138 [Abstract] [Full Text]