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Rheumatology Advance Access originally published online on February 28, 2003
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Rheumatology 2003; 42: 528-533
© 2003 British Society for Rheumatology

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

A. W. Morgan1,2,, V. H. Keyte2, S. J. Babbage2, J. I. Robinson2, F. Ponchel2, J. H. Barrett3, B. B. Bhakta1, S. J. Bingham1, M. H. Buch1, P. G. Conaghan1, A. Gough1, M. Green1, C. A. Lawson1,2, C. T. Pease1, A. F. Markham2, W. E. R. Ollier4, P. Emery1, J. Worthington4 and J. D. Isaacs1,2

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

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.

Correspondence to: A. W. Morgan, Molecular Medicine Unit, Clinical Sciences Building, St. James's University Hospital, Leeds, LS9 7TF, UK. E-mail: a.w.morgan{at}leeds.ac.uk


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