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

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Abstract

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. The Journal of Rheumatology

Original languageEnglish
Pages (from-to)740-746
Number of pages7
JournalJournal of Rheumatology
Volume37
Issue number4
DOIs
Publication statusPublished - 2010 Apr 1

Fingerprint

Epitopes
Rheumatoid Arthritis
Tumor Necrosis Factor-alpha
Alleles
Carrier State
Rheumatology
Therapeutics
Odds Ratio
Genotype

Keywords

  • Responsiveness
  • Rheumatoid arthritis
  • Shared epitope
  • Tumor necrosis factor-α inhibitors
  • Tumor necrosis factor-α polymorphism

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Immunology and Allergy

Cite this

@article{9838fec0d89c4829a1d0e2a262c2342e,
title = "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",
abstract = "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. The Journal of Rheumatology",
keywords = "Responsiveness, Rheumatoid arthritis, Shared epitope, Tumor necrosis factor-α inhibitors, Tumor necrosis factor-α polymorphism",
author = "Lee, {Young Ho} and Ji, {Jong Dae} and Bae, {Sang Cheol} and Song, {Gwan Gyu}",
year = "2010",
month = "4",
day = "1",
doi = "10.3899/jrheum.090707",
language = "English",
volume = "37",
pages = "740--746",
journal = "Journal of Rheumatology",
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TY - JOUR

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

T2 - A metaanalysis update

AU - Lee, Young Ho

AU - Ji, Jong Dae

AU - Bae, Sang Cheol

AU - Song, Gwan Gyu

PY - 2010/4/1

Y1 - 2010/4/1

N2 - 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. The Journal of Rheumatology

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. The Journal of Rheumatology

KW - Responsiveness

KW - Rheumatoid arthritis

KW - Shared epitope

KW - Tumor necrosis factor-α inhibitors

KW - Tumor necrosis factor-α polymorphism

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U2 - 10.3899/jrheum.090707

DO - 10.3899/jrheum.090707

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