Association of TNF-alpha –308 G/A polymorphism with responsiveness to TNF-α-blockers in rheumatoid arthritis: a meta-analysis

Tumor necrosis factor (TNF) antagonists are among the most effective therapies for rheumatoid arthritis (RA), yet not all patients show a response. Using meta-analysis, this present study was designed to investigate whether or not the TNF-α promoter –308 A/G polymorphism is associated with responsiveness to anti-TNF therapy in RA patients. We performed an exhaustive search for studies that examined the association of the TNF-α promoter –308 A/G polymorphism and responsiveness of anti-TNF therapy in RA using MEDLINE citations and manual review. Meta-analysis was performed for A allele carrier (genotypes A/A + A/G) between responders to anti-TNF therapy and a non-responder group in a random effects model. A total of 6 studies met the inclusion criteria. The number of patients in individual studies ranged from 33 to 123. There were 311 RA patients who were included in this meta-analysis. There was no heterogeneity between studies (I2 = 0%, P = 0.42). The overall OR for the A allele carrier status was significantly decreased in the responder group (OR = 0.33, 95% confidence interval = 0.17–0.63, P = 0.0008). The frequency of the A allele carrier was 53/240 (22.1%) in responders and 32/71 (45.1%) in non-responders. Patients not responding to anti-TNF therapy showed an increased frequency of the A allele. The meta-analysis of the available data shows a significant association between the TNF-α promoter –308 A/G polymorphism and responsiveness to anti-TNF therapy, suggesting that the individuals with RA who carry the A allele have a poorer response to anti-TNF therapy than those with the G allele.