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

INTRODUCTION: 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 a...

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Autores principales: García-Lozano, José-Raúl, Torres-Agrela, Belén, Montes-Cano, Marco-Antonio, Ortiz-Fernández, Lourdes, Conde-Jaldón, Marta, Teruel, María, García, Alicia, Núñez-Roldán, Antonio, Martín, Javier, González-Escribano, María-Francisca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3672784/
https://www.ncbi.nlm.nih.gov/pubmed/23320549
http://dx.doi.org/10.1186/ar4141
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author García-Lozano, José-Raúl
Torres-Agrela, Belén
Montes-Cano, Marco-Antonio
Ortiz-Fernández, Lourdes
Conde-Jaldón, Marta
Teruel, María
García, Alicia
Núñez-Roldán, Antonio
Martín, Javier
González-Escribano, María-Francisca
author_facet García-Lozano, José-Raúl
Torres-Agrela, Belén
Montes-Cano, Marco-Antonio
Ortiz-Fernández, Lourdes
Conde-Jaldón, Marta
Teruel, María
García, Alicia
Núñez-Roldán, Antonio
Martín, Javier
González-Escribano, María-Francisca
author_sort García-Lozano, José-Raúl
collection PubMed
description INTRODUCTION: 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, p(c )= 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, p(c )= 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).
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spelling pubmed-36727842013-06-10 Association of the AIRE gene with susceptibility to rheumatoid arthritis in a European population: a case control study García-Lozano, José-Raúl Torres-Agrela, Belén Montes-Cano, Marco-Antonio Ortiz-Fernández, Lourdes Conde-Jaldón, Marta Teruel, María García, Alicia Núñez-Roldán, Antonio Martín, Javier González-Escribano, María-Francisca Arthritis Res Ther Research Article INTRODUCTION: 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, p(c )= 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, p(c )= 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). BioMed Central 2013 2013-01-15 /pmc/articles/PMC3672784/ /pubmed/23320549 http://dx.doi.org/10.1186/ar4141 Text en Copyright © 2013 García-Lozano et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
García-Lozano, José-Raúl
Torres-Agrela, Belén
Montes-Cano, Marco-Antonio
Ortiz-Fernández, Lourdes
Conde-Jaldón, Marta
Teruel, María
García, Alicia
Núñez-Roldán, Antonio
Martín, Javier
González-Escribano, María-Francisca
Association of the AIRE gene with susceptibility to rheumatoid arthritis in a European population: a case control study
title Association of the AIRE gene with susceptibility to rheumatoid arthritis in a European population: a case control study
title_full Association of the AIRE gene with susceptibility to rheumatoid arthritis in a European population: a case control study
title_fullStr Association of the AIRE gene with susceptibility to rheumatoid arthritis in a European population: a case control study
title_full_unstemmed Association of the AIRE gene with susceptibility to rheumatoid arthritis in a European population: a case control study
title_short Association of the AIRE gene with susceptibility to rheumatoid arthritis in a European population: a case control study
title_sort association of the aire gene with susceptibility to rheumatoid arthritis in a european population: a case control study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3672784/
https://www.ncbi.nlm.nih.gov/pubmed/23320549
http://dx.doi.org/10.1186/ar4141
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