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Preferential Association of Interferon Regulatory Factor 5 Gene Variants with Seronegative Rheumatoid Arthritis in 2 Swedish Case-Control Studies

Objective. Two interferon regulatory factor 5 (IRF5) gene variants were examined for association with rheumatoid arthritis (RA). Methods. A total of 2300 patients with RA and 1836 controls were recruited from 2 independent RA studies in Sweden. One insertion-deletion polymorphism (CGGGG indel) and one single-nucleotide polymorphism (rs10488631) in the IRF5 gene were genotyped and analyzed within RA subgroups stratified by rheumatoid factor (RF) and anticitrullinated peptide antibodies (ACPA). Results. The CGGGG indel was preferentially associated with the RF-negative (OR 1.29, p = 7.9 × 10−5) and ACPA-negative (OR 1.27, p = 7.3 × 10−5) RA subgroups compared to the seropositive counterparts. rs10488631 was exclusively associated within the seronegative RA subgroups (RF-negative: OR 1.24, p = 0.016; ACPA-negative: OR 1.27, p = 4.1 × 10−3). Conclusion. Both the CGGGG indel and rs10488631 are relevant for RA susceptibility, especially for seronegative RA.