White Rose University Consortium logo
University of Leeds logo University of Sheffield logo York University logo

Association of FCGR3A and FCGR3B haplotypes with rheumatoid arthritis and primary Sjögren's syndrome [POSTER PRESENTATION]

Mackie, S., Robinson, J.I., Barrett, J.H., Lawson, C.A., Martin, S., Haroon-Rashid, L., Cooper, D., Bowman, S.J., Pease, C.T., Conaghan, P.G., Green, M., Quinn, M., Isaacs, J.D., Emery, P. and Morgan, A.W. (2005) Association of FCGR3A and FCGR3B haplotypes with rheumatoid arthritis and primary Sjögren's syndrome [POSTER PRESENTATION]. Arthritis Research and Therapy, 7 (Suppl ). p. 121. ISSN 1478-6362

Full text available as:
[img] Text
ar1642.pdf
Available under licence : See the attached licence file.

Download (1498Kb)

Abstract

Background

Rheumatoid arthritis (RA) is an autoimmune disease that is thought to arise from a complex interaction between multiple genetic factors and environmental triggers. We have previously demonstrated an association between a Fc gamma receptor (FcγR) haplotype and RA in a cross-sectional cohort of RA patients. We have sought to confirm this association in an inception cohort of RA patients and matched controls. We also extended our study to investigate a second autoanti-body associated rheumatic disease, primary Sjögren's syndrome (PSS).

Methods

The FCGR3A-158F/V and FCGR3B-NA1/NA2 functional polymorphisms were examined for association in an inception cohort of RA patients (n = 448), and a well-characterised PSS cohort (n = 83) from the United Kingdom. Pairwise disequilibrium coefficients (D') were calculated in 267 Blood Service healthy controls. The EHPlus program was used to estimate haplotype frequencies for patients and controls and to determine whether significant linkage disequilibrium was present. A likelihood ratio test is performed to test for differences between the haplotype frequencies in cases and controls. A permutation procedure implemented in this program enabled 1000 permutations to be performed on all haplotype associations to assess significance.

Results

There was significant linkage disequilibrium between FCGR3A and FCGR3B (D' = -0.445, P = 0.001). There was no significant difference in the FCGR3A or FCGR3B allele or genotype frequencies in the RA or PSS patients compared with controls. However, there was a significant difference in the FCGR3A-FCGR3B haplotype distributions with increased homozygosity for the FCGR3A-FCGR3B 158V-NA2 haplotype in both our inception RA cohort (odds ratio = 2.15, 95% confidence interval = 1.1–4.2 P = 0.027) and PSS (odds ratio = 2.83, 95% confidence interval = 1.0–8.2, P = 0.047) compared with controls. The reference group for these analyses comprised individuals who did not possess a copy of the FCGR3A-FCGR3B 158V-NA2 haplotype.

Conclusions

We have confirmed our original findings of association between the FCGR3A-FCGR3B 158V-NA2 haplotype and RA in a new inception cohort of RA patients. This suggests that there may be an RA-susceptibility gene at this locus. The significant increased frequency of an identical haplotype in PSS suggests the FcγR genetic locus may contribute to the pathogenesis of diverse autoantibody-mediated rheumatic diseases.

Item Type: Article
Copyright, Publisher and Additional Information: © 2005 BioMed Central Ltd. Poster presentation from 25th European Workshop for Rheumatology Research Glasgow, UK. 24-27 February 2005.
Institution: The University of Leeds
Academic Units: The University of Leeds > Faculty of Medicine and Health (Leeds) > Institute of Molecular Medicine (LIMM) (Leeds) > Section of Musculoskeletal Disease (Leeds)
The University of Leeds > Faculty of Medicine and Health (Leeds) > Institute of Molecular Medicine (LIMM) (Leeds) > Section of Genetics (Leeds)
Depositing User: Repository Officer
Date Deposited: 13 Mar 2006
Last Modified: 08 Jun 2014 23:28
Published Version: http://arthritis-research.com/content/7/S1/P121
Status: Published
Refereed: Yes
Identification Number: 10.1186/ar1642
URI: http://eprints.whiterose.ac.uk/id/eprint/1054

Actions (login required)

View Item View Item