{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T18:34:40Z","timestamp":1781548480430,"version":"3.54.5"},"reference-count":38,"publisher":"The Journal of Rheumatology","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Rheumatol"],"published-print":{"date-parts":[[2015,8]]},"abstract":"<jats:sec><jats:title>Objective.<\/jats:title><jats:p>Rheumatoid arthritis (RA) that is negative for anticitrullinated protein antibodies (ACPA) is a subentity of RA, characterized by less severe disease. At the individual level, however, considerable differences in the severity of joint destruction occur. We performed a study on genetic factors underlying the differences in joint destruction in ACPA-negative patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods.<\/jats:title><jats:p>A genome-wide association study was done with 262 ACPA-negative patients with early RA included in the Leiden Early Arthritis Clinic and related to radiographic joint destruction over 7 years. Significant single-nucleotide polymorphisms (SNP) were evaluated for association with progression of radiographic joint destruction in 253 ACPA-negative patients with early RA included in the Better Anti-Rheumatic Farmaco Therapy (BARFOT) study. According to the Bonferroni correction of the number of tested SNP, the threshold for significance was p &lt; 2 \u00d7 10<jats:sup>\u22127<\/jats:sup> in phase 1 and 0.0045 in phase 2. In both cohorts, joint destruction was measured by Sharp\/van der Heijde method with good reproducibility.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results.<\/jats:title><jats:p>Thirty-three SNP associated with severity of joint destruction (p &lt; 2 \u00d7 10<jats:sup>\u22127<\/jats:sup>) in phase 1. In phase 2, rs2833522 (p = 0.0049) showed borderline significance. A combined analysis of both the Leiden and BARFOT datasets of rs2833522 confirmed this association with joint destruction (p = 3.57 \u00d7 10<jats:sup>\u22129<\/jats:sup>); the minor allele (A) associated with more severe damage (for instance, after 7 yrs followup, patients carrying AA had 1.22 times more joint damage compared to patients carrying AG and 1.50 times more joint damage than patients carrying GG). <jats:italic>In silico<\/jats:italic> analysis using the ENCODE and Ensembl databases showed presence of H3K4me3 histone mark, transcription factors, and long noncoding RNA in the region of rs2833522, an intergenic SNP located between <jats:italic>HUNK<\/jats:italic> and <jats:italic>SCAF4<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion.<\/jats:title><jats:p>Rs2833522 might be associated with the severity of joint destruction in ACPA-negative RA.<\/jats:p><\/jats:sec>","DOI":"10.3899\/jrheum.140741","type":"journal-article","created":{"date-parts":[[2015,6,16]],"date-time":"2015-06-16T01:12:55Z","timestamp":1434417175000},"page":"1383-1391","source":"Crossref","is-referenced-by-count":27,"title":["Genetic Factors for the Severity of ACPA-negative Rheumatoid Arthritis in 2 Cohorts of Early Disease: A Genome-wide Study"],"prefix":"10.3899","volume":"42","author":[{"given":"Diederik P.C.","family":"de Rooy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roula","family":"Tsonaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria 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