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Are gene polymorphisms related to treatment outcomes of methotrexate in patients with rheumatoid arthritis? A systematic review and meta-analysis.
Pharmacogenomics 2017; 18(2):175-195P

Abstract

AIM

Identifying the predictors of responsiveness and adverse events in methotrexate (MTX) treated patients with rheumatoid arthritis (RA) has been the focus of most concern, but still without consistent consensus.

METHODS

PubMed and OVID EMBASE were searched to collect relevant studies that addressed correlations between gene polymorphisms and efficacy and/or toxicity in MTX-treated RA patients. Allelic, recessive, dominant and over-dominant model were applied.

RESULTS

A total of 68 studies were included. For associations with efficacy, AMPD1 34C>T polymorphism was related to responsiveness in dominant model (odds ratio [OR]: 1.77; 95% CI: 1.19-2.63) and over-dominant model (OR: 1.59; 95% CI: 1.04-2.45). ATIC T675C polymorphism had association with responsiveness in recessive model (OR: 2.54; 95% CI: 1.23-5.26). For associations with toxicity, polymorphisms in TYMS 1494 del6 and FPGS rs10106 were correlated to absenting overall adverse events in recessive model (OR: 0.68; 95% CI: 0.49-0.95) and dominant model (OR: 0.54; 95% CI: 0.35-0.83) respectively while MTHFR C677T was associated with presenting overall adverse events in allelic model (OR: 1.29; 95% CI: 1.02-1.63), recessive model (OR: 1.38; 95% CI: 1.00-1.89) and dominant model (OR: 1.41; 95% CI: 1.02-1.94).

CONCLUSION

Polymorphisms in AMPD1 34C>T and ATIC T675C predict responsiveness. The absence of TYMS 1494 del6 and FPGS rs10106 and presence of MTHFR C677T predict adverse events in RA patients treated with MTX. Moreover, variations of the associations were found between Caucasians and non-Caucasians.

Authors+Show Affiliations

Department of Rheumatology & Immunology, West China Hospital, Sichuan University, Chengdu, China.Department of Medical Record & Statistics, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Affiliated Hospital of University of Electronic Science & Technology, Chengdu, China.Department of Rheumatology & Immunology, West China Hospital, Sichuan University, Chengdu, China.Department of Rheumatology & Immunology, West China Hospital, Sichuan University, Chengdu, China.Department of Rheumatology & Immunology, West China Hospital, Sichuan University, Chengdu, China.

Pub Type(s)

Journal Article
Meta-Analysis
Review
Systematic Review

Language

eng

PubMed ID

27992285

Citation

Chen, Yuehong, et al. "Are Gene Polymorphisms Related to Treatment Outcomes of Methotrexate in Patients With Rheumatoid Arthritis? a Systematic Review and Meta-analysis." Pharmacogenomics, vol. 18, no. 2, 2017, pp. 175-195.
Chen Y, Zou K, Sun J, et al. Are gene polymorphisms related to treatment outcomes of methotrexate in patients with rheumatoid arthritis? A systematic review and meta-analysis. Pharmacogenomics. 2017;18(2):175-195.
Chen, Y., Zou, K., Sun, J., Yang, Y., & Liu, G. (2017). Are gene polymorphisms related to treatment outcomes of methotrexate in patients with rheumatoid arthritis? A systematic review and meta-analysis. Pharmacogenomics, 18(2), pp. 175-195. doi:10.2217/pgs-2016-0158.
Chen Y, et al. Are Gene Polymorphisms Related to Treatment Outcomes of Methotrexate in Patients With Rheumatoid Arthritis? a Systematic Review and Meta-analysis. Pharmacogenomics. 2017;18(2):175-195. PubMed PMID: 27992285.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Are gene polymorphisms related to treatment outcomes of methotrexate in patients with rheumatoid arthritis? A systematic review and meta-analysis. AU - Chen,Yuehong, AU - Zou,Kun, AU - Sun,Jianhong, AU - Yang,Yuan, AU - Liu,Gang, Y1 - 2016/12/19/ PY - 2016/12/20/pubmed PY - 2017/8/5/medline PY - 2016/12/20/entrez KW - efficacy KW - meta-analysis KW - methotrexate KW - polymorphisms KW - rheumatoid arthritis KW - toxicity SP - 175 EP - 195 JF - Pharmacogenomics JO - Pharmacogenomics VL - 18 IS - 2 N2 - AIM: Identifying the predictors of responsiveness and adverse events in methotrexate (MTX) treated patients with rheumatoid arthritis (RA) has been the focus of most concern, but still without consistent consensus. METHODS: PubMed and OVID EMBASE were searched to collect relevant studies that addressed correlations between gene polymorphisms and efficacy and/or toxicity in MTX-treated RA patients. Allelic, recessive, dominant and over-dominant model were applied. RESULTS: A total of 68 studies were included. For associations with efficacy, AMPD1 34C>T polymorphism was related to responsiveness in dominant model (odds ratio [OR]: 1.77; 95% CI: 1.19-2.63) and over-dominant model (OR: 1.59; 95% CI: 1.04-2.45). ATIC T675C polymorphism had association with responsiveness in recessive model (OR: 2.54; 95% CI: 1.23-5.26). For associations with toxicity, polymorphisms in TYMS 1494 del6 and FPGS rs10106 were correlated to absenting overall adverse events in recessive model (OR: 0.68; 95% CI: 0.49-0.95) and dominant model (OR: 0.54; 95% CI: 0.35-0.83) respectively while MTHFR C677T was associated with presenting overall adverse events in allelic model (OR: 1.29; 95% CI: 1.02-1.63), recessive model (OR: 1.38; 95% CI: 1.00-1.89) and dominant model (OR: 1.41; 95% CI: 1.02-1.94). CONCLUSION: Polymorphisms in AMPD1 34C>T and ATIC T675C predict responsiveness. The absence of TYMS 1494 del6 and FPGS rs10106 and presence of MTHFR C677T predict adverse events in RA patients treated with MTX. Moreover, variations of the associations were found between Caucasians and non-Caucasians. SN - 1744-8042 UR - https://www.unboundmedicine.com/medline/citation/27992285/Are_gene_polymorphisms_related_to_treatment_outcomes_of_methotrexate_in_patients_with_rheumatoid_arthritis_A_systematic_review_and_meta_analysis_ L2 - http://www.futuremedicine.com/doi/full/10.2217/pgs-2016-0158?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -