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Rheumatology Advance Access published online on February 28, 2003
Rheumatology, doi:10.1093/rheumatology/keg169
Rheumatology © British Society for Rheumatology 2003; all rights reserved
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© 2003 British Society for Rheumatology

Original Papers

Fc{gamma}RIIIA-158V and rheumatoid arthritis: a confirmation study

A. W. Morgan 1*, V. H. Keyte 2, S. J. Babbage 2, J. I. Robinson 2, F. Ponchel 2, J. H. Barrett 3, B. B. Bhakta 4, S. J. Bingham 4, M. H. Buch 4, P. G. Conaghan 4, A. Gough 4, M. Green 4, C. A. Lawson 1, C. T. Pease 4, A. F. Markham 2, W. E. R. Ollier 5, P. Emery 4, J. Worthington 5, J. D. Isaacs 1

1 Rheumatology and Rehabilitation Research Unit, University of Leeds; Molecular Medicine Unit, University of Leeds
2 Molecular Medicine Unit, University of Leeds
3 Cancer Research UK, Genetic Epidemiology Division, University of Leeds
4 Rheumatology and Rehabilitation Research Unit, University of Leeds
5 ARC Epidemiology Unit, University of Manchester, UK

* Corresponding author. E-mail: a.w.morgan{at}leeds.ac.uk.

Received 25 January 2002 ; accepted 6 November 2002

Abstract

Objectives. To develop a robust assay for genotyping the Fc{gamma}RIIIA-158V/F polymorphism and to confirm the putative association between the Fc{gamma}RIIIA-158V allele and rheumatoid arthritis (RA).

Methods. This allelic association study examined the Fc{gamma}RIIIA-158V/F polymorphism for association with RA. A novel single-stranded conformational polymorphism assay was used to genotype 828 RA patients and 581 controls from the UK.

Results. The Fc{gamma}RIIIA-158V allele was associated with both RA (P=0.02) and nodules (P=0.04). Individuals homozygous for this higher affinity allele had a significantly increased risk of RA (OR 1.53, 95% CI 1.08-2.18) and the development of nodules (OR 2.20, 95% CI 1.20-4.01). There was no evidence of an interaction with the shared epitope.

Conclusions. We have developed a novel assay to genotype the Fc{gamma}RIIIA-158F/V polymorphism and confirmed that homozygosity for the Fc{gamma}RIIIA-158V allele is associated with UK Caucasian RA, particularly in those individuals with nodules, suggesting Fc{gamma}RIIIA may play a role in determining disease severity or in the development of nodules per se.

Key words: Fc gamma receptor, Rheumatoid arthritis, HLA-DRB1, Polymorphisms.
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