RT Journal Article
SR Electronic
T1 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
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP jrheum.090707
DO 10.3899/jrheum.090707
A1 Young Ho Lee
A1 Jong Dae Ji
A1 Sang-Cheol Bae
A1 Gwan Gyu Song
YR 2010
UL http://www.jrheum.org/content/early/2010/02/24/jrheum.090707.abstract
AB Objective To investigate whether tumor necrosis factor-α (TNF-α) 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-α promoter –308 and –238 A/G 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-α –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-α –308 A/G polymorphism and responsiveness to TNF blockers. The overall metaanalysis showed that the TNF-α –238 A/G polymorphism was not associated with the responsiveness of RA patients to TNF blockers, and stratification by TNF blocker revealed that the TNF-α –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-α –238 A/G polymorphism, but no associations between treatment response and the TNF-α –308 A/G polymorphism or SE status.