Associations Between Tumor Necrosis Factor-α (TNF-α)-308 and-238 G/A Polymorphisms and Shared Epitope Status and Responsiveness to TNF-α Blockers in Rheumatoid Arthritis: A Metaanalysis Update

Objective. To investigate whether tumor necrosis factor-alpha (TNF-alpha) promoter -308 A/G and -238 A/G polymorphisms and shared epitope (SE) status are associated with responsiveness to anti-TNF therapy in patients with rheumatoid arthritis (RA). Methods. A comparative metaanalysis was conducted on A allele carriers (genotypes A/A + A/G) of the TNF-alpha promoter -308 and -238 A/C polymorphisms and SE status in responders and nonresponders to anti-TNF therapy. Results. A total of 13 studies were included in the metaanalysis. Metaanalysis showed that the TNF-alpha -308 A/G polymorphism is not associated with responsiveness to TNF blockers in RA patients. Studies with a small number of subjects (< 100) showed that the odds ratio for the A allele carrier state was significantly lower among responders (OR 0.344, 95% CI 0.152-0.779, p = 0.01). Studies with a higher number of subjects (>= 100) found no association between the TNF-alpha +308 A/C polymorphism and responsiveness to TNF blockers. The overall metaanalysis showed that the TNF-alpha -238 A/C polymorphism was not associated with the responsiveness of RA patients to TNF blockers, and stratification by TNF blocker revealed that the TNF-alpha 238 A/G polymorphism was associated with response of infliximab (OR 0.441, 95% CI 0.203-0.609, p = 0.039). SE status was found not to be associated with response to TNF blockers. Conclusion. Metaanalysis of available data revealed an association between treatment response to infliximab and the TNF-alpha -238 A/C polymorphism, but no associations between treatment response and the TNF-alpha -308 A/G polymorphism or SE status. (First Release March 1 2010; J Rheumatol 2010;37:740-6; doi:10.3899/jrheum.090707)