TY - JOUR
T1 - Association of FcgR2a, but Not FcgR3a, with Inflammatory Bowel Diseases Across Three Caucasian Populations
AU - Weersma, Rinse K.
AU - Crusius, J. Bart A.
AU - Roberts, Rebecca L.
AU - Koeleman, Bobby P. C.
AU - Palomino-Morales, Rogelio
AU - Wolfkamp, Simone
AU - Hollis-Moffatt, Jade E.
AU - Festen, Eleonora A. M.
AU - Meisneris, Sander
AU - Heijmans, Roel
AU - Noble, Colin L.
AU - Gearry, Richard B.
AU - Barclay, Murrary L.
AU - Gomez-Garcia, Maria
AU - Lopez-Nevot, Miguel A.
AU - Nieto, Antonio
AU - Rodrigo, Luis
AU - Radstake, Timothy R. D. J.
AU - van Bodegraven, Adriaan A.
AU - Wijmenga, Cisca
AU - Merriman, Tony R.
AU - Stokkers, Pieter C. F.
AU - Pena, A. Salvador
AU - Martin, Javier
AU - Alizadeh, Behrooz Z.
N1 - Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.
PY - 2010/12
Y1 - 2010/12
N2 - Background: The Fc receptors II and III (FcgR2a, and FcgR3a) play a crucial role in the regulation of the immune response. The FcgR2a*519GG and FcgR3a*559CC genotypes have been associated with several autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, nephritis, and possibly to type I diabetes, and celiac disease. In a large multicenter, two-stage study of 6570 people, we tested whether the FcgR2a and FcgR3a genes were also involved in inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC).Methods: We genotyped the FcgR2a*A519G and FcgR3a*A559C functional variants in 4205 IBD patients in six well-phenotyped Caucasian IBD cohorts and 2365 ethnically matched controls recruited from the Netherlands, Spain, and New Zealand.Results: In the initial Dutch study we found a significant association of FcgR2a genotypes with IBD (P-genotype = 0.02); while the FcgR2a*519GG was more common in controls (23%) than in IBD patients (18%; odds ratio [OR] = 0.75; 95% confidence interval [CI] 0.61-0.92; P = 0.004). This association was corroborated by a combined analysis across all the study populations (Mantel-Haenszel [MN] OR = 0.84; 0.74-0.95; P = 0.005) in the next stage. The Fcgr2a*GG genotype was associated with both UC (MH-OR = 0.84; 0.72-0.97; P = 0.01) and CD (MH-OR = 0.84; 0.73-0.97; P = 0.01), suggesting that this genotype confers a protective effect against IBD. There was no association of FcgR3a*A559C genotypes with IBD, CD, or UC in any of the three studied populations.Conclusions: The FcgR2a*519G functional variant was associated with IBD and reduced susceptibility to UC and to CD in Caucasians. There was no association between FcgR3a*5A559C and IBD, CD or UC.
AB - Background: The Fc receptors II and III (FcgR2a, and FcgR3a) play a crucial role in the regulation of the immune response. The FcgR2a*519GG and FcgR3a*559CC genotypes have been associated with several autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, nephritis, and possibly to type I diabetes, and celiac disease. In a large multicenter, two-stage study of 6570 people, we tested whether the FcgR2a and FcgR3a genes were also involved in inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC).Methods: We genotyped the FcgR2a*A519G and FcgR3a*A559C functional variants in 4205 IBD patients in six well-phenotyped Caucasian IBD cohorts and 2365 ethnically matched controls recruited from the Netherlands, Spain, and New Zealand.Results: In the initial Dutch study we found a significant association of FcgR2a genotypes with IBD (P-genotype = 0.02); while the FcgR2a*519GG was more common in controls (23%) than in IBD patients (18%; odds ratio [OR] = 0.75; 95% confidence interval [CI] 0.61-0.92; P = 0.004). This association was corroborated by a combined analysis across all the study populations (Mantel-Haenszel [MN] OR = 0.84; 0.74-0.95; P = 0.005) in the next stage. The Fcgr2a*GG genotype was associated with both UC (MH-OR = 0.84; 0.72-0.97; P = 0.01) and CD (MH-OR = 0.84; 0.73-0.97; P = 0.01), suggesting that this genotype confers a protective effect against IBD. There was no association of FcgR3a*A559C genotypes with IBD, CD, or UC in any of the three studied populations.Conclusions: The FcgR2a*519G functional variant was associated with IBD and reduced susceptibility to UC and to CD in Caucasians. There was no association between FcgR3a*5A559C and IBD, CD or UC.
KW - FcgR2a
KW - FcgR3a
KW - Crohn's disease
KW - ulcerative colitis
KW - genome-wide association study
KW - SYSTEMIC-LUPUS-ERYTHEMATOSUS
KW - GENOME-WIDE ASSOCIATION
KW - GAMMA RECEPTOR-IIA
KW - CIRCULATING IMMUNE-COMPLEXES
KW - ACTIVE CROHNS-DISEASE
KW - TOLL-LIKE RECEPTORS
KW - RHEUMATOID-ARTHRITIS
KW - ULCERATIVE-COLITIS
KW - AUTOIMMUNE-DISEASES
KW - NEW-ZEALAND
U2 - 10.1002/ibd.21342
DO - 10.1002/ibd.21342
M3 - Article
C2 - 20848524
SN - 1078-0998
VL - 16
SP - 2080
EP - 2089
JO - Inflammatory Bowel Diseases
JF - Inflammatory Bowel Diseases
IS - 12
ER -