English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/3446
Title: Association of FCGR2A and FCGR2A-FCGR3A haplotypes with susceptibility to giant cell arteritis
Authors: Morgan, Ann W.; Robinson, Jim I.; Barrett, Jennifer H.; Martín, J.; Walker, Amy; Babbage, Sarah J.; Ollier, W. E. R.; González-Gay, M. A.; Isaacs, John D.
Issue Date: 17-Jul-2006
Publisher: BioMed Central
Citation: Arthritis Research & Therapy 2006, 8:R109
Abstract: The Fc gamma receptors have been shown to play important roles in the initiation and regulation of many immunological and inflammatory processes and to amplify and refine the immune response to an infection. We have investigated the hypothesis that polymorphism within the FCGR genetic locus is associated with giant cell arteritis (GCA). Biallelic polymorphisms in FCGR2A, FCGR3A, FCGR3B and FCGR2B were examined for association with biopsy-proven GCA (n = 85) and healthy ethnically matched controls (n = 132) in a well-characterised cohort from Lugo, Spain. Haplotype frequencies and linkage disequilibrium (D') were estimated across the FCGR locus and a model-free analysis performed to determine association with GCA. There was a significant association between FCGR2A- 131RR homozygosity (odds ratio (OR) 2.10, 95% confidence interval (CI) 1.12 to 3.77, P = 0.02, compared with all others) and carriage of FCGR3A-158F (OR 3.09, 95% CI 1.10 to 8.64, P = 0.03, compared with non-carriers) with susceptibility to GCA. FCGR haplotypes were examined to refine the extent of the association. The haplotype showing the strongest association with GCA susceptibility was the FCGR2AFCGR3A 131R-158F haplotype (OR 2.84, P = 0.01 for homozygotes compared with all others). There was evidence of a multiplicative joint effect between homozygosity for FCGR2A- 131R and HLA-DRB1*04 positivity, consistent with both of these two genetic factors contributing to the risk of disease. The risk of GCA in HLA-DRB1*04 positive individuals homozygous for the FCGR2A-131R allele is increased almost six-fold compared with those with other FCGR2A genotypes who are HLA-DRB1*04 negative. We have demonstrated that FCGR2A may contribute to the 'susceptibility' of GCA in this Spanish population. The increased association observed with a FCGR2A-FCGR3A haplotype suggests the presence of additional genetic polymorphisms in linkage disequilibrium with this haplotype that may contribute to disease susceptibility. These findings may ultimately provide new insights into disease pathogenesis.
Description: This article is online at: http://arthritis-research.com/content/8/4/R109
URI: http://hdl.handle.net/10261/3446
ISSN: 1465-9913
DOI: 10.1186/ar1996
Appears in Collections:(IPBLN) Artículos
Files in This Item:
File Description SizeFormat 
ar1996.pdf149,99 kBAdobe PDFThumbnail
Show full item record

WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.