Open Access Open Badges Research article

Association of the AIRE gene with susceptibility to rheumatoid arthritis in a European population: a case control study

José-Raúl García-Lozano1, Belén Torres-Agrela1, Marco-Antonio Montes-Cano1, Lourdes Ortiz-Fernández1, Marta Conde-Jaldón1, María Teruel2, Alicia García3, Antonio Núñez-Roldán1, Javier Martín2 and María-Francisca González-Escribano1*

Author Affiliations

1 Servicio de Inmunología, Hospital Universitario Virgen del Rocío (IBiS, CSIC, US), Avenida Manuel Siurot s/n, 41013-Sevilla, Spain

2 Instituto de Parasitología y Biomedicina "López Neyra", CSIC, Parque Tecnológico de Ciencias de la Salud, Avenida del Conocimiento s/n, Armilla, 18100-Granada, Spain

3 Unidad de Reumatología, Hospital Universitario Virgen del Rocío, Avenida Manuel Siurot s/n, 41013-Sevilla, Spain

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Arthritis Research & Therapy 2013, 15:R11  doi:10.1186/ar4141

Published: 15 January 2013



AIRE is a transcriptional regulator playing a functional role in thymocyte education and negative selection by controlling the expression of peripheral antigens in the thymus. Recently, the AIRE gene was identified as a genetic risk factor for rheumatoid arthritis (RA) in genome wide association (GWA) studies performed in the Japanese population. According to the available data this association is restricted to the Asian population. However, different facts could influence the lack of association in Caucasian populations. The aim of this study was to further investigate the possible role of the AIRE gene in susceptibility to RA in a Caucasian population.


A total of 472 Spanish Caucasian RA patients and 475 ethnically matched controls were included in the study. Three single-nucleotide polymorphisms (SNPs) (rs2776377, rs878081 and rs1055311) with a minor allele frequency >0.05 in the Caucasian population which were not included in the high-throughput platforms used in the GWA studies performed in susceptibility to RA, and two SNPs (rs2075876 and rs1800520) associated with RA in the Japanese population, were selected and genotyped using TaqMan assays.


No significant differences in the distribution of the alleles of rs2776377, rs2075876, rs1055311 and rs1800520 SNPs between RA patients and controls were observed. Nevertheless, the frequency of the C allele of rs878081 was significantly higher among RA patients (80.5% vs. 74.6% in the control group, pc = 0.012, OR = 1.41, 95%CI 1.13-1.75). Regarding the distribution of the rs878081 genotypes, a higher frequency of CC homozygous individuals was found in the RA patient group (65.56% vs. 56.47% in the control group, pc = 0.013, OR = 1.47, 95%CI 1.12-1.93). The in silico analysis predicted lower affinity to the binding-site of a motif of the transcription NF-κB family and lower transcription levels of AIRE gene for the rs878081C risk variant


Our findings suggest that the AIRE gene is associated with susceptibility to RA in the Spanish population. Probably, this association has not been detected in the European population in the GWA studies because the earliest high-throughput platforms did not include SNP suitable markers (e.g. rs878081).