Research article
Analysis of TNFAIP3, a feedback inhibitor of nuclear factor-κB and the neighbor intergenic 6q23 region in rheumatoid arthritis susceptibility
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* Corresponding author: Antonio Gonzalez anlugon@hotmail.com
1 Laboratorio de Investigacion 2 and Rheumatology Unit, Hospital Clinico Universitario de Santiago, Santiago de Compostela, 15706, Spain
2 Rheumatology Unit, Hospital La Paz, Madrid, 28046, Spain
3 Laboratorio de Investigación Osteoarticular y del Envejecimiento, Servicio de Reumatología, Hospital Universitario Juan Canalejo, A Coruña, 15006, Spain
4 Arthritis Unit, Rheumatology Department, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi I Sunyer, Barcelona, 08036, Spain
5 Rheumatology Unit, Hospital Universitario Virgen de las Nieves, Granada, 18001, Spain
6 Rheumatology Unit, Hospital Universitario Gregorio Marañon, Madrid, 28007, Spain
7 Rheumatology Unit, Hopital Santa Creu e San Pau, Barcelona, 08025, Spain
8 Rheumatology Unit, Hospital Clinico San Carlos, Madrid, 28040, Spain
9 Rheumatology Unit, Hospital Universitario La Princesa, Madrid, 28006, Spain
10 Rheumatology Unit, Fundación Jimenez Diaz, Madrid, 28040, Spain
11 Rheumatology Unit, Hospital 12 de Octubre, Madrid, 28041, Spain
12 Rheumatology Unit, Hospital Universitario de Bellvitge, Barcelona, 08907, Spain
13 Rheumatology Unit, Hospital Univesitario Virgen Macarena, Sevilla, 41003, Spain
14 Rheumatology Unit, Hospital Universitario de Valme, Sevilla, 41014, Spain
15 Department of Medicine, University of Santiago de Compostela, Santiago de Compostela, 15705, Spain
Arthritis Research & Therapy 2009, 11:R42 doi:10.1186/ar2650
Published: 17 March 2009Abstract
Introduction
Genome-wide association studies of rheumatoid arthritis (RA) have identified an association of the disease with a 6q23 region devoid of genes. TNFAIP3, an RA candidate gene, flanks this region, and polymorphisms in both the TNFAIP3 gene and the intergenic region are associated with systemic lupus erythematosus. We hypothesized that there is a similar association with RA, including polymorphisms in TNFAIP3 and the intergenic region.
Methods
To test this hypothesis, we selected tag-single nucleotide polymorphisms (SNPs) in both loci. They were analyzed in 1,651 patients with RA and 1,619 control individuals of Spanish ancestry.
Results
Weak evidence of association was found both in the 6q23 intergenic region and in the TNFAIP3 locus. The rs582757 SNP and a common haplotype in the TNFAIP3 locus exhibited association with RA. In the intergenic region, two SNPs were associated, namely rs609438 and rs13207033. The latter was only associated in patients with anti-citrullinated peptide antibodies. Overall, statistical association was best explained by the interdependent contribution of SNPs from the two loci TNFAIP3 and the 6q23 intergenic region.
Conclusions
Our data are consistent with the hypothesis that several RA genetic factors exist in the 6q23 region, including polymorphisms in the TNFAIP3 gene, like that previously described for systemic lupus erythematosus.