Assoziation des ABCB1-C3435T-Polymorphismus mit dem Ansprechen auf DMARDs sowie deren Toxizität bei rheumatoider Arthritis: Eine Metaanalyse

Translated title of the contribution: Association of the ABCB1 C3435T polymorphism with responsiveness to and toxicity of DMARDs in rheumatoid arthritis: A meta-analysis

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Objective: The aim of this study was to investigate whether the C3435T polymorphism in the gene encoding multidrug resistance protein 1 (ABCB1) can predict responsiveness to or toxicity of disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA). Methods: We conducted a meta-analysis of studies on the association between the ABCB1 C3435T polymorphism and nonresponsiveness to or toxicity of DMARDs in RA patients, using the PUBMED and EMBASE electronic citation databases. Subsequent inclusion/exclusion procedures were performed and then data were extracted for association analysis. Results: A total of 14 comparison studies from 9 articles met our inclusion criteria. This final group comprised 4 studies containing data on associations between the ABCB1 C3435T polymorphism and RA susceptibility, 5 studies on the response to DMARDs, and 5 on toxicity of DMARDs in RA patients according to ABCB1 polymorphism status. Meta-analysis revealed no association between RA susceptibility and the ABCB1 C3435T polymorphism [odds ratio (OR) for the T allele = 0.948, 95 % confidence interval (CI) 0.756–1.189, p = 0.645]. Meta-analysis showed no association between the ABCB1 C3435T T allele and a nonresponse to DMARD therapy (OR 0.952, 95 % CI 0.516–1.685, p = 0.817). Stratification by DMARD type indicated no association between the ABCB1 C3435T T allele and nonresponse to methotrexate (MTX) treatment (OR 1.201, 95 % CI 0.456–3.164, p = 0.711). However, the analysis did indicate that MTX toxicity was associated with the ABCB1 C3435T polymorphism in RA under an overdominant model (TC vs. TT + CC; OR 0.483, 95 % CI 0.259–0.900, p = 0.022), evidencing a lower risk of MTX toxicity for heterozygotes (TC) than homozygotes (TT and CC). Conclusion: This meta-analysis demonstrated that the ABCB1 C3435T polymorphism may be not associated with responsiveness to DMARD therapy, but may be associated with MTX toxicity in RA.

Original languageGerman
Pages (from-to)707-715
Number of pages9
JournalZeitschrift fur Rheumatologie
Volume75
Issue number7
DOIs
Publication statusPublished - 2016 Sep 1

Fingerprint

Antirheumatic Agents
Meta-Analysis
Rheumatoid Arthritis
Methotrexate
Odds Ratio
Confidence Intervals
Alleles
MDR Genes
Drug Therapy
Homozygote
Heterozygote
Drug-Related Side Effects and Adverse Reactions
Databases

Keywords

  • Autoimmune diseases
  • Disease-modifying, antirheumatic drugs
  • Methotrexate
  • Polymorphism, genetic
  • Side effects

ASJC Scopus subject areas

  • Rheumatology

Cite this

@article{1a148e8192dd4ab0878fa2198fca4190,
title = "Assoziation des ABCB1-C3435T-Polymorphismus mit dem Ansprechen auf DMARDs sowie deren Toxizit{\"a}t bei rheumatoider Arthritis: Eine Metaanalyse",
abstract = "Objective: The aim of this study was to investigate whether the C3435T polymorphism in the gene encoding multidrug resistance protein 1 (ABCB1) can predict responsiveness to or toxicity of disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA). Methods: We conducted a meta-analysis of studies on the association between the ABCB1 C3435T polymorphism and nonresponsiveness to or toxicity of DMARDs in RA patients, using the PUBMED and EMBASE electronic citation databases. Subsequent inclusion/exclusion procedures were performed and then data were extracted for association analysis. Results: A total of 14 comparison studies from 9 articles met our inclusion criteria. This final group comprised 4 studies containing data on associations between the ABCB1 C3435T polymorphism and RA susceptibility, 5 studies on the response to DMARDs, and 5 on toxicity of DMARDs in RA patients according to ABCB1 polymorphism status. Meta-analysis revealed no association between RA susceptibility and the ABCB1 C3435T polymorphism [odds ratio (OR) for the T allele = 0.948, 95 {\%} confidence interval (CI) 0.756–1.189, p = 0.645]. Meta-analysis showed no association between the ABCB1 C3435T T allele and a nonresponse to DMARD therapy (OR 0.952, 95 {\%} CI 0.516–1.685, p = 0.817). Stratification by DMARD type indicated no association between the ABCB1 C3435T T allele and nonresponse to methotrexate (MTX) treatment (OR 1.201, 95 {\%} CI 0.456–3.164, p = 0.711). However, the analysis did indicate that MTX toxicity was associated with the ABCB1 C3435T polymorphism in RA under an overdominant model (TC vs. TT + CC; OR 0.483, 95 {\%} CI 0.259–0.900, p = 0.022), evidencing a lower risk of MTX toxicity for heterozygotes (TC) than homozygotes (TT and CC). Conclusion: This meta-analysis demonstrated that the ABCB1 C3435T polymorphism may be not associated with responsiveness to DMARD therapy, but may be associated with MTX toxicity in RA.",
keywords = "Autoimmune diseases, Disease-modifying, antirheumatic drugs, Methotrexate, Polymorphism, genetic, Side effects",
author = "Lee, {Young Ho} and Bae, {S. C.} and Song, {Gwan Gyu}",
year = "2016",
month = "9",
day = "1",
doi = "10.1007/s00393-015-1618-x",
language = "German",
volume = "75",
pages = "707--715",
journal = "Zeitschrift fur Rheumatologie",
issn = "0340-1855",
publisher = "D. Steinkopff-Verlag",
number = "7",

}

TY - JOUR

T1 - Assoziation des ABCB1-C3435T-Polymorphismus mit dem Ansprechen auf DMARDs sowie deren Toxizität bei rheumatoider Arthritis

T2 - Eine Metaanalyse

AU - Lee, Young Ho

AU - Bae, S. C.

AU - Song, Gwan Gyu

PY - 2016/9/1

Y1 - 2016/9/1

N2 - Objective: The aim of this study was to investigate whether the C3435T polymorphism in the gene encoding multidrug resistance protein 1 (ABCB1) can predict responsiveness to or toxicity of disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA). Methods: We conducted a meta-analysis of studies on the association between the ABCB1 C3435T polymorphism and nonresponsiveness to or toxicity of DMARDs in RA patients, using the PUBMED and EMBASE electronic citation databases. Subsequent inclusion/exclusion procedures were performed and then data were extracted for association analysis. Results: A total of 14 comparison studies from 9 articles met our inclusion criteria. This final group comprised 4 studies containing data on associations between the ABCB1 C3435T polymorphism and RA susceptibility, 5 studies on the response to DMARDs, and 5 on toxicity of DMARDs in RA patients according to ABCB1 polymorphism status. Meta-analysis revealed no association between RA susceptibility and the ABCB1 C3435T polymorphism [odds ratio (OR) for the T allele = 0.948, 95 % confidence interval (CI) 0.756–1.189, p = 0.645]. Meta-analysis showed no association between the ABCB1 C3435T T allele and a nonresponse to DMARD therapy (OR 0.952, 95 % CI 0.516–1.685, p = 0.817). Stratification by DMARD type indicated no association between the ABCB1 C3435T T allele and nonresponse to methotrexate (MTX) treatment (OR 1.201, 95 % CI 0.456–3.164, p = 0.711). However, the analysis did indicate that MTX toxicity was associated with the ABCB1 C3435T polymorphism in RA under an overdominant model (TC vs. TT + CC; OR 0.483, 95 % CI 0.259–0.900, p = 0.022), evidencing a lower risk of MTX toxicity for heterozygotes (TC) than homozygotes (TT and CC). Conclusion: This meta-analysis demonstrated that the ABCB1 C3435T polymorphism may be not associated with responsiveness to DMARD therapy, but may be associated with MTX toxicity in RA.

AB - Objective: The aim of this study was to investigate whether the C3435T polymorphism in the gene encoding multidrug resistance protein 1 (ABCB1) can predict responsiveness to or toxicity of disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA). Methods: We conducted a meta-analysis of studies on the association between the ABCB1 C3435T polymorphism and nonresponsiveness to or toxicity of DMARDs in RA patients, using the PUBMED and EMBASE electronic citation databases. Subsequent inclusion/exclusion procedures were performed and then data were extracted for association analysis. Results: A total of 14 comparison studies from 9 articles met our inclusion criteria. This final group comprised 4 studies containing data on associations between the ABCB1 C3435T polymorphism and RA susceptibility, 5 studies on the response to DMARDs, and 5 on toxicity of DMARDs in RA patients according to ABCB1 polymorphism status. Meta-analysis revealed no association between RA susceptibility and the ABCB1 C3435T polymorphism [odds ratio (OR) for the T allele = 0.948, 95 % confidence interval (CI) 0.756–1.189, p = 0.645]. Meta-analysis showed no association between the ABCB1 C3435T T allele and a nonresponse to DMARD therapy (OR 0.952, 95 % CI 0.516–1.685, p = 0.817). Stratification by DMARD type indicated no association between the ABCB1 C3435T T allele and nonresponse to methotrexate (MTX) treatment (OR 1.201, 95 % CI 0.456–3.164, p = 0.711). However, the analysis did indicate that MTX toxicity was associated with the ABCB1 C3435T polymorphism in RA under an overdominant model (TC vs. TT + CC; OR 0.483, 95 % CI 0.259–0.900, p = 0.022), evidencing a lower risk of MTX toxicity for heterozygotes (TC) than homozygotes (TT and CC). Conclusion: This meta-analysis demonstrated that the ABCB1 C3435T polymorphism may be not associated with responsiveness to DMARD therapy, but may be associated with MTX toxicity in RA.

KW - Autoimmune diseases

KW - Disease-modifying, antirheumatic drugs

KW - Methotrexate

KW - Polymorphism, genetic

KW - Side effects

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U2 - 10.1007/s00393-015-1618-x

DO - 10.1007/s00393-015-1618-x

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C2 - 26184955

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VL - 75

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JO - Zeitschrift fur Rheumatologie

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