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Open Access item Association of FCGR2A and FCGR2A-FCGR3A haplotypes with susceptibility to giant cell arteritis
|Authors:||Morgan, Ann W.|
Robinson, Jim I.
Barrett, Jennifer H.
Babbage, Sarah J.
Ollier, W. E. R.
González-Gay, M. A.
Isaacs, John D.
|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
|Description:||This article is online at: http://arthritis-research.com/content/8/4/R109|
|Appears in Collections:||(IPBLN) Artículos|
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