Associations between tumor necrosis factor-alpha (TNF-alpha) -308 and -238 G/A polymorphisms and shared epitope status and responsiveness to TNF-alpha 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/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-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 (>or= 100) found no association between the TNF-alpha -308 A/G polymorphism and responsiveness to TNF blockers. The overall metaanalysis showed that the TNF-alpha -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-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.


CONCLUSIONS
Metaanalysis of available data revealed an association between treatment response to infliximab and the TNF-alpha -238 A/G polymorphism, but no associations between treatment response and the TNF-alpha -308 A/G polymorphism or SE status.
Lee
Young Ho
YH
Division of Rheumatology, Department of Internal Medicine, Korea University Medical Center, Korea University College of Medicine, Seoul, Korea. lyhcgh@korea.ac.kr
Ji
Jong Dae
JD
Bae
Sang-Cheol
SC
Song
Gwan Gyu
GG
D000483:Alleles; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000628:therapy*; D000939:Epitopes / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D000069285:Infliximab; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics*
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D000939:Epitopes; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab