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Identification of IRX1 as a risk locus for rheumatoid factor positivity in rheumatoid arthritis in a genome-wide association study

Abstract: Objective. Rheumatoid factor (RF) is a wellestablished diagnostic and prognostic biomarker in rheumatoid arthritis (RA). However, ~20% of RA patients are negative for this anti-IgG antibody. To date, only variation at the HLA?DRB1 gene has been associated with the presence of RF. This study was undertaken to identify additional genetic variants associated with RF positivity. Methods. A genome-wide association study (GWAS) for RF positivity was performed using an Illumina Quad610 genotyping platform. A total of 937 RF-positive and 323 RF-negative RA patients were genotyped for >550,000 single-nucleotide polymorphisms (SNPs). Association testing was performed using an allelic chi-square test implemented in Plink software. An independent cohort of 472 RF-positive and 190 RF-negative RA patients was used to validate the most significant findings. Results. In the discovery stage, a SNP in the IRX1 locus on chromosome 5p15.3 (SNP rs1502644) showed a genome-wide significant association with RF positivity (P 5 4.13 3 1028, odds ratio [OR] 0.37 [95% confidence interval (95% CI) 0.26?0.53]). In the validation stage, the association of IRX1 with RF was replicated in an independent group of RA patients (P 5 0.034, OR 0.58 [95% CI 0.35?0.97] and combined P 5 1.14 3 1028, OR 0.43 [95% CI 0.32?0.58]). Conclusion. To our knowledge, this is the first GWAS of RF positivity in RA. Variation at the IRX1 locus on chromosome 5p15.3 is associated with the presence of RF. Our findings indicate that IRX1 and HLA? DRB1 are the strongest genetic factors for RF production in RA.

 Fuente: Arthritis and Rheumatology, 2016, 68(6), 1384-1391

 Publisher: John Wiley and Sons Ltd

 Publication date: 01/06/2016

 No. of pages: 8

 Publication type: Article

 DOI: 10.1002/art.39591

 ISSN: 2326-5205,2326-5191

Authorship

JULIÁ, ANTONIO

BLANCO, FRANCISCO

FERNÁNDEZ GUTIÉRREZ, BENJAMÍN

GONZÁLEZ, ANTONIO

CAÑETE, JUAN D.

MAYMÓ, JOAN

ALPERI LÓPEZ, MERCEDES

OLIVÉ, ALEX

COROMINAS, HÉCTOR

GONZÁLEZ ÁLVARO, ISIDORO

FERNÁNDEZ NEBRO, ANTONIO

ERRA, ALBA

SÁNCHEZ FERNÁNDEZ, SIMÓN

ALONSO, ARNALD

LÓPEZ LASANTA, MARÍA

TORTOSA, RAÚL

CODÓ, LAIA

GELPI, JOSEP LLUIS

GARCÍA MONTERO, ANDRÉS C.