{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T15:42:01Z","timestamp":1767973321835,"version":"3.49.0"},"reference-count":70,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2006,3,29]],"date-time":"2006-03-29T00:00:00Z","timestamp":1143590400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2006,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine whether the tumor necrosis factor \u03b1 (<jats:italic>TNFA<\/jats:italic>) \u2013308 guanine\u2010to\u2010adenosine polymorphism and\/or the shared epitope (SE) is associated with radiographic damage in patients with early rheumatoid arthritis (RA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The cohort consisted of 189 patients with early seropositive RA (median 5.6 months since symptom onset) who had active disease, no previous disease\u2010modifying antirheumatic drug treatment, and \u22652 sets of scored radiographs of the hands\/wrists and forefeet. <jats:italic>TNFA<\/jats:italic> \u2013308 polymorphism was analyzed by polymerase chain reaction pyrosequencing. The SE was defined as presence of any 1 of the following HLA\u2013DRB1 alleles: *0101, *0102, *0401, *0404, *0405, *0408, *0410, *1001, *1402, or *1406. Radiographic progression was assessed by the total Sharp score.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Using a weighted least\u2010squares regression analysis, patients with the \u2013308 <jats:italic>TNFA<\/jats:italic> AA plus AG genotypes (n = 49) had significantly higher rates of progression in erosion scores (median 0.84 versus 0.48 units\/year), joint space narrowing (JSN) scores (0.42 versus 0.04), and total Sharp scores (1.70 versus 0.61) compared with patients with the <jats:italic>TNFA<\/jats:italic> GG genotype (n = 140). Presence of the SE (n = 137) was associated with significantly lower progression rates (per year) for total Sharp scores (median 0.9 versus 1.25 units\/year) and JSN scores (0.04 versus 0.41), but not for erosion scores (0.50 versus 0.61) compared with patients without the SE (n = 52). In a least\u2010squares multiple linear regression model, the presence of the AA plus AG genotypes was associated with a significantly higher progression rate after adjusting for the presence of the SE, interaction between the SE and the AA plus AG genotypes, baseline log C\u2010reactive protein level, Health Assessment Questionnaire Disability Index, total Sharp score, swollen joint count, and presence of osteophytes (osteoarthritis). There was a strong linkage disequilibrium between DRB1*0301 and <jats:italic>TNFA<\/jats:italic> polymorphism (D\u2032 = 0.84, r<jats:sup>2<\/jats:sup> = 0.45, <jats:italic>P<\/jats:italic> &lt; 0.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study showed an association between the <jats:italic>TNFA<\/jats:italic> \u2013308 polymorphism and progression of radiographic damage in patients with early seropositive RA. This association appeared to be independent of the SE, but might be dependent on other genetic variants in linkage disequilibrium with the \u2013308 <jats:italic>TNFA<\/jats:italic> A allele and DRB1*0301. Further studies should be conducted to validate these results in both longitudinal observational cohorts and randomized clinical trials.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.21750","type":"journal-article","created":{"date-parts":[[2006,3,30]],"date-time":"2006-03-30T02:47:36Z","timestamp":1143686856000},"page":"1105-1116","source":"Crossref","is-referenced-by-count":39,"title":["Association of tumor necrosis factor \u03b1 polymorphism, but not the shared epitope, with increased radiographic progression in a seropositive rheumatoid arthritis inception 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