title: Association of the AIRE gene with susceptibility to rheumatoid arthritis in a European population: a case control study.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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
  
  
  CONCLUSIONS
  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).
authors: José-Raúl
authors: JR
authors: García-Lozano
authors: Belén
authors: B
authors: Torres-Agrela
authors: Marco-Antonio
authors: MA
authors: Montes-Cano
authors: Lourdes
authors: L
authors: Ortiz-Fernández
authors: Marta
authors: M
authors: Conde-Jaldón
authors: María
authors: M
authors: Teruel
authors: Alicia
authors: A
authors: García
authors: Antonio
authors: A
authors: Núñez-Roldán
authors: Javier
authors: J
authors: Martín
authors: María-Francisca
authors: MF
authors: González-Escribano
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics*; D016022:Case-Control Studies; D005060:Europe; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics*; D044465:White People / Q000235:genetics; D000096927:AIRE Protein
chemical_list: D014157:Transcription Factors; D000096927:AIRE Protein