title: Association of TNF-alpha -308 G/A polymorphism with responsiveness to TNF-alpha-blockers in rheumatoid arthritis: a meta-analysis.
abstract: 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-alpha 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-alpha 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 (I (2) = 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-alpha 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.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Korea University Medical Center, 126-1 Ka, Anam-Dong, Seongbuk-Ku, Seoul 136-705, South Korea. lyhcgh@korea.ac.kr
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Lee
authors.forename: Young Hee
authors.initials: YH
authors.lastname: Rho
authors.forename: Seong Jae
authors.initials: SJ
authors.lastname: Choi
authors.forename: Jong Dae
authors.initials: JD
authors.lastname: Ji
authors.forename: Gwan Gyu
authors.initials: GG
authors.lastname: Song
mesh_terms: D018501:Antirheumatic Agents / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D020641:Polymorphism, Single Nucleotide; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000235:genetics*
chemical_list: D018501:Antirheumatic Agents; D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha