Analysis of TNFAIP3, a feedback inhibitor of nuclear factor-kappa B and the neighbor intergenic 6q23 region in rheumatoid arthritis susceptibility
Por:
Dieguez-Gonzalez, R, Calaza, M, Perez-Pampin, E, Balsa, A, Blanco, FJ, Canete, JD, Caliz, R, Carreno, L, de la Serna, AR, Fernandez-Gutierrez, B, Ortiz, AM, Herrero-Beaumont, G, Pablos, JL, Narvaez, J, Navarro, F, Marenco, JL, Gomez-Reino, JJ, Gonzalez, A
Publicada:
1 ene 2009
Resumen:
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.
Filiaciones:
Dieguez-Gonzalez, R:
Univ Santiago, Hosp Clin, Lab Invest 2, Santiago De Compostela 15706, Spain
Univ Santiago, Hosp Clin, Rheumatol Unit, Santiago De Compostela 15706, Spain
Calaza, M:
Univ Santiago, Hosp Clin, Lab Invest 2, Santiago De Compostela 15706, Spain
Univ Santiago, Hosp Clin, Rheumatol Unit, Santiago De Compostela 15706, Spain
Perez-Pampin, E:
Univ Santiago, Hosp Clin, Lab Invest 2, Santiago De Compostela 15706, Spain
Univ Santiago, Hosp Clin, Rheumatol Unit, Santiago De Compostela 15706, Spain
Balsa, A:
Hosp La Paz, Rheumatol Unit, Madrid 28046, Spain
Blanco, FJ:
Hosp Univ Juan Canalejo, Serv Reumatol, Lab Invest Osteoarticular & Envejecimiento, La Coruna 15006, Spain
Canete, JD:
Hosp Clin Barcelona, Inst Invest Biomed August Pi Sunyer, Arthritis Unit, Dept Rheumatol, Barcelona 08036, Spain
Caliz, R:
Hosp Univ Virgen de las Nieves, Rheumatol Unit, Granada 18001, Spain
Carreno, L:
Hosp Univ Gregorio Maranon, Rheumatol Unit, Madrid 28007, Spain
de la Serna, AR:
Hop Santa Creu & San Pau, Rheumatol Unit, Barcelona 08025, Spain
Fernandez-Gutierrez, B:
Hosp Clin San Carlos, Rheumatol Unit, Madrid 28040, Spain
Ortiz, AM:
Hosp Univ Princesa, Rheumatol Unit, Madrid 28006, Spain
Herrero-Beaumont, G:
Fdn Jimenez Diaz, Rheumatol Unit, Madrid 28040, Spain
Pablos, JL:
Hosp 12 Octubre, Rheumatol Unit, E-28041 Madrid, Spain
Narvaez, J:
Hosp Univ Bellvitge, Rheumatol Unit, Barcelona 08907, Spain
Navarro, F:
Hosp Univ Virgen Macarena, Rheumatol Unit, Seville 41003, Spain
Marenco, JL:
Hosp Univ Valme, Rheumatol Unit, Seville 41003, Spain
Gomez-Reino, JJ:
Univ Santiago, Hosp Clin, Lab Invest 2, Santiago De Compostela 15706, Spain
Univ Santiago, Hosp Clin, Rheumatol Unit, Santiago De Compostela 15706, Spain
Univ Santiago de Compostela, Dept Med, Santiago De Compostela 15705, Spain
Gonzalez, A:
Univ Santiago, Hosp Clin, Lab Invest 2, Santiago De Compostela 15706, Spain
Univ Santiago, Hosp Clin, Rheumatol Unit, Santiago De Compostela 15706, Spain
Gold, Green Published
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