Skip Navigation



Human Molecular Genetics Advance Access published online on July 25, 2007
Human Molecular Genetics, doi:10.1093/hmg/ddm194
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
16/21/2552    most recent
ddm194v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Alizadeh, B. Z.
Right arrow Articles by Koeleman, B. P.C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Alizadeh, B. Z.
Right arrow Articles by Koeleman, B. P.C.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Association analysis of functional variants of the FcgRIIa and FcgRIIIa genes with type 1 diabetes, celiac disease and rheumatoid arthritis

Behrooz Z. Alizadeh1,2,*, Gustavo Valdigem1, Marieke J. H. Coenen3, Alexandra Zhernakova1, Barbara Franke3, Alienke Monsuur1, Piet L. C. M. van Riel4, Pilar Barrera4, Timothy R. D. J. Radstake4, Bart. O. Roep2, Cisca Wijmenga1,5 and Bobby P.C. Koeleman 1,2

1 Complex Genetics Section, Dept. of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands 2 Dept. of Immunohematology & Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands 3 Dept. of Anthropogenetics, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands 4 Dept. of Rheumatology and Experimental Rheumatology and Advanced Therapeutics, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands 5 Dept. of Genetics, University Medical Center Groningen, the Netherlands

* Correspondence to: Behrooz Z. Alizadeh, MD, PhD Complex Genetics Section, Department of Medical Genetics, University Medical Center Utrecht, PO Box 85060, 3508 AB Utrecht, the Netherlands. Tel: +31-30-2537925, Fax: +31-30-2538479. E-mail: b.z.alizadeh{at}umcutrecht.nl

Received June 7, 2007; Revised July 14, 2007; Accepted July 14, 2007

Background FcgRIIa and FcgRIIIa are potent modulators of the immune system which bind (auto)antibodies and activate immune cells. The FcgRIIa*A519G and FcgRIIIa* A559C functional variants have been associated with several immune-related diseases. We studied FcgRIIa*A519G and FcgRIIIa*A559C SNPs in type 1 diabetes (T1D), celiac disease (CD), and rheumatoid arthritis (RA) patients and controls, and included a meta-analysis of all recent studies of FcgRIIIa*A559C and RA.

Method Our cohorts comprised 350 T1D, 519 CD, 639 RA patients and 1,359 controls, who were genotyped for FcgRIIa*A519G and FcgRIIIa*A559C variants. Regression and EM-algorithm-based haplotype analyses were used for the data analysis.

Results We found significant differences in genotype frequencies of FcgRIIa between controls and patients with T1D (P=0.04), CD (P=0.000005) and RA (P=0.04). The FcgRIIa*519GG genotype showed an increased risk for both T1D (OR=1.51; 95%CI=1.08-2.12; P=0.015), and CD (OR=1.81, 95%CI=1.35-2.37; P=0.000004), but not for RA. There was no difference in the frequency of FcgRIIIa*A559C genotypes or allelotypes between controls with T1D, CD, and RA. We found that FcgRIIa and FcgRIIIa haplotypes frequencies differed significantly between controls and patients with T1D (P=0.05), and with CD (P=0.00038), but not with RA patients. Our meta-analysis showed a significant 1.37(1.14-1.66) fold increased risk of RA for the FcgRIIIa*559CC (158VV) genotype (P=0.001).

Conclusion This is the first report that the FcgRIIa*519GG genotype predisposes to T1D and CD. We confirmed the FcgRIIIa*559CC genotype is associated to RA. If replicated, our findings would suggest the FcgRIIa*519G as a common risk factor for auto-immune diseases. This may have clinical implications with regard to efficacy or safety of antibody-based immuno-modulator therapies


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.