Association of FcgR2a, but not FcgR3a, with inflammatory bowel diseases across three Caucasian populations

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 po...

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Published in:Inflammatory bowel diseases Vol. 16; no. 12; pp. 2080 - 2089
Main Authors: Weersma, Rinse K., Crusius, J. Bart A., Roberts, Rebecca L., Koeleman, Bobby P.C., Palomino‐Morales, Rogelio, Wolfkamp, Simone, Hollis‐Moffatt, Jade E., Festen, Eleonora A.M., Meisneris, Sander, Heijmans, Roel, Noble, Colin L., Gearry, Richard B., Barclay, Murrary L., Gómez‐Garcia, María, Lopez‐Nevot, Miguel A., Nieto, Antonio, Rodrigo, Luis, Radstake, Timothy R.D.J., van Bodegraven, Adriaan A., Wijmenga, Cisca, Merriman, Tony R., Stokkers, Pieter C.F., Peña, A. Salvador, Martín, Javier, Alizadeh, Behrooz Z.
Format: Journal Article
Language:English
Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-12-2010
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Summary: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 [MH] 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. (Inflamm Bowel Dis 2010)
Bibliography:These authors contributed equally.
Supported by the Health Research Council of New Zealand, the Plan Nacional de I+D+I, Spain (grant SAF2006‐00398), and the Junta de Andalucía, Spain (grant CTS1880). B.Z.A. is supported by the Netherlands Organization for Health Research and Development (ZonMw, grant number 016.096.121). R.L.R. is the recipient of a New Zealand Sir Charles Hercus Health Research Fellowship, and J.H.M. is the recipient of a New Zealand National Heart Foundation Postdoctoral Research Fellowship. R.W. is supported by a clinical fellow grant from the Netherlands Organization for Scientific Research (NWO).
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ISSN:1078-0998
1536-4844
1536-4844
DOI:10.1002/ibd.21342