RT Journal Article
T1 Identification of IRX1 as a Risk Locus for Rheumatoid Factor Positivity in Rheumatoid Arthritis in a Genome-Wide Association Study.
A1 Julia, Antonio
A1 Blanco, Francisco
A1 Fernandez-Gutierrez, Benjamin
A1 Gonzalez, Antonio
A1 Cañete, Juan D
A1 Maymo, Joan
A1 Alperi-Lopez, Mercedes
A1 Olive, Alex
A1 Corominas, Hector
A1 Martinez-Taboada, Victor
A1 Gonzalez-Alvaro, Isidoro
A1 Fernandez-Nebro, Antonio
A1 Erra, Alba
A1 Sanchez-Fernandez, Simon
A1 Alonso, Arnald
A1 Lopez-Lasanta, Maria
A1 Tortosa, Raul
A1 Codo, Laia
A1 Lluis-Gelpi, Josep
A1 Garcia-Montero, Andres C
A1 Bertranpetit, Jaume
A1 Absher, Devin
A1 Myers, Richard M
A1 Tornero, Jesus
A1 Marsal, Sara
K1 Arthritis, Rheumatoid
K1 Genetic Loci
K1 Genetic Variation
K1 Genome-Wide Association Study
AB Rheumatoid factor (RF) is a well-established 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. 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. 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 = 4.13 × 10(-8) , 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 = 0.034, OR 0.58 [95% CI 0.35-0.97] and combined P = 1.14 × 10(-8) , OR 0.43 [95% CI 0.32-0.58]). 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.
PB Wiley
YR 2016
FD 2016-05-26
LK http://hdl.handle.net/10668/9780
UL http://hdl.handle.net/10668/9780
LA en
NO Julià A, Blanco F, Fernández-Gutierrez B, González A, Cañete JD, Maymó J, et al. Identification of IRX1 as a Risk Locus for Rheumatoid Factor Positivity in Rheumatoid Arthritis in a Genome-Wide Association Study. Arthritis Rheumatol. 2016 Jun;68(6):1384-91
DS RISalud
RD Mar 14, 2025