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.

Abstract

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.

CONCLUSION:

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.

• Authors: Young Ho Lee, Jong Dae Ji, Sang-Cheol Bae, Gwan Gyu Song
• Journal: The Journal of rheumatology (J Rheumatol) Vol. 37 Issue 4 Pg. 740-6 (Apr 2010) ISSN: 0315-162X [Print] Canada
• PMID: 20194454 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antirheumatic Agents
• Epitopes
• Tumor Necrosis Factor-alpha
• Infliximab

Topics

• Alleles
• Antibodies, Monoclonal (therapeutic use)
• Antirheumatic Agents (therapeutic use)
• Arthritis, Rheumatoid (genetics, therapy)
• Epitopes (genetics)
• Genetic Predisposition to Disease
• Genotype
• Humans
• Infliximab
• Polymorphism, Single Nucleotide
• Treatment Outcome
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, genetics)