Association of tumor necrosis factor α polymorphism, but not the shared epitope, with increased radiographic progression in a seropositive rheumatoid arthritis inception cohort

Abstract

Objective. To determine whether the tumor necrosis factor ␣ (TNFA) -308 guanine-to-adenosine polymorphism and/or the shared epitope (SE) is associated with radiographic damage in patients with early rheumatoid arthritis (RA).Methods. The cohort consisted of 189 patients with early seropositive RA (median 5.6 months since symptom onset) who had active disease, no previous disease-modifying antirheumatic drug treatment, and >2 sets of scored radiographs of the hands/wrists and forefeet. TNFA -308 polymorphism was analyzed by polymerase chain reaction pyrosequencing. The SE was defined as presence of any 1 of the following HLA-DRB1 alleles: *0101, *0102, *0401, *0404, *0405, *0408, *0410, *1001, *1402, or *1406. Radiographic progression was assessed by the total Sharp score.Results. Using a weighted least-squares regression analysis, patients with the -308 TNFA 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 TNFA 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-squares 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-reactive protein level, Health Assessment Questionnaire Disability Index, total Sharp score, swollen joint count, and presence of osteophytes (osteoarthritis). There was a strong linkage disequili-

Association of Tumor Necrosis Factor-Alpha -308 G>A Polymorphism With Rheumatoid Arthritis in Two North Indian Cohorts

“…This finding was in line with other studies from populations of France, America, Taiwan and Netherlands which have also reported higher percentage of female RA patients (78%, 75.7%, 75.4%, and 73.5%, respectively). 36,[38][39][40] The results implied that sex may have a significant effect on susceptibility to RA, with the disease being three times more frequent in females than in males. Moreover, it has been reported that hypoandrogenicity is responsible for RA in younger women.…”

Genetic Polymorphisms Modifying Oxidative Stress Are Associated with Disease Activity in Rheumatoid Arthritis Patients

“…Previous clinical studies investigated the influence of SNPs in TNFA promoter on the severity of RA and reported contradictory results. Most studies suggest an association of TNFA -308A allele with a higher disease severity [30][31][32], while others found worst radiographic damage in the patients with TNFA -308GG genotype [33]. A more severe disease in the carriers of TNFA -308GA genotype was observed [34] however, in other studies no association of TNFA G-308A allele with the absence of erosions or between bone destruction was reported [28,35,36].…”

Linkage and Association Studies of Joint Morbidity from Rheumatoid Arthritis

“…The occurrence of RA has also been consistently associated with HLA-linked genes, as well as tumor necrosis factor, HLA-B, PADI4, CTLA4, TRAF1, STAT4, and PTPN22 [34][35][36][37][38] . Currently, genome projects have resulted not only in identification of genetic factors affecting health and disease but also in improved prediction and care for several diseases.…”