Genetic studies in rheumatoid arthritis

D. M. Grennan and P. A. Sanders1

Rheumatology Unit, Wrightington Hospital and
1 Department of Rheumatology, Withington Hospital, Wigan, Lancashire, UK

SIR, Definition of susceptibility genes in rheumatic diseases [1] is also complicated by heterogeneity of the diseases themselves. In a series of studies published between 1985 and 1990 we showed that rheumatoid arthritis was genetically heterogeneous. As Lanchbury and coworkers seem unaware of these studies we summarize the evidence here.

  1. HLA haplotype sharing by affected sibling pairs is affected by the DR4 status of the proband and by presence or absence of autoimmune thyroid disease in the sibship [2].
  2. There are associations between rheumatoid disease and immunoglobulin heavy chain variants coded for by genes on chromosome 14 in DR4-positive but not in DR4-negative rheumatoid arthritis subsets [3].
  3. There are different HLA haplotype associations in articular compared with extra-articular rheumatoid disease subsets [4].

This genetic heterogeneity is important to those trying to define susceptibility genes to rheumatoid disease in the future and we suggest that future linkage studies be stratified as suggested above to consider DR4 status, presence or absence of autoimmune thyroid disease and presence or absence of extra-articular disease.

Notes

Correspondence to: D. M. Grennan. E-mail: sal43uk{at}yahoo.co.uk Back

References

  1. Lanchbury J, Hall M, Steer S. Progress and problems in defining susceptibility genes for rheumatic diseases. Rheumatology 2002;41:361–4.[Free Full Text]
  2. Grennan D M, Sanders P, Dyer P, Harris R. HLA haplotype sharing by siblings with rheumatoid arthritis: Evidence for genetic heterogeneity. Ann Rheum Dis 1986;45:126–9.[Abstract]
  3. Sanders P, De Lange G, Dyer P, Grennan D. Gm and Km allotypes in rheumatoid arthritis. Ann Rheum Dis 1985;44:529–33.[Abstract]
  4. Hillarby C, Clarkson R, Grennan D et al. Immunogenetic heterogeneity in rheumatoid disease as characterized by different MHC associations (DQ, Dw, C4) in articular and extra-articular subsets. Br J Rheumatol 1990;30:529.
Accepted 27 August 2002





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