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Reduced folate carrier-1 80G>A polymorphism affects methotrexate treatment outcome in rheumatoid arthritis.
Pharmacogenomics J 2007; 7(6):404-7PJ

Abstract

The folate antagonist methotrexate (MTX) is a drug currently used in the treatment of rheumatoid arthritis (RA). MTX enters the cells through the reduced folate carrier (RFC-1) and is activated to polyglutamates. Previous studies have shown that RFC-1 expression may influence the efficacy of therapy with MTX. The studies suggest that G80A polymorphism in RFC-1 is associated with altered folate/antifolate levels and the subjects carrying homozygous mutant 80AA genotype tend to have higher plasma folate and MTX concentrations and higher erythrocyte polyglutamate levels compared with those with the wild type or heterozygous genotype. It is possible that this polymorphism might influence MTX treatment outcome in patients with RA. In the present study, we examined the association between RFC-1 G80A polymorphism and treatment outcome in patients with RA administered MTX. The study was carried out on 174 patients diagnosed with RA treated with MTX (7.5-15.0 mg weekly) plus low doses of methylprednisone. The RFC-1 80G>A polymorphism (resulting in a histidine-to-arginine substitution at codon 27 of RFC-1) was detected using a polymerase chain reaction-restriction fragment length polymorphism method. The probability of remission of RA symptoms was 3.32-fold higher in carriers of 80AA genotype as compared with patients with 80GG genotype (P=0.021, OR=3.32, 95% CI: 1.26-8.79). The frequency of A allele among MTX responders was 62.1, compared to 47.8% in a group of poor MTX responders (P=0.013, OR=1.78, 95% CI: 1.13-2.81). Moreover, the increase of aminotransferase activity was noted more frequently in carriers of 80AA genotype. The present data suggest that evaluation of RFC-1 gene 80G>A polymorphism may be a useful tool to optimize MTX therapy in patients with RA.

Authors+Show Affiliations

Department of Pharmacology, Pomeranian Medical University, Szczecin, Poland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17325736

Citation

Drozdzik, M, et al. "Reduced Folate Carrier-1 80G>A Polymorphism Affects Methotrexate Treatment Outcome in Rheumatoid Arthritis." The Pharmacogenomics Journal, vol. 7, no. 6, 2007, pp. 404-7.
Drozdzik M, Rudas T, Pawlik A, et al. Reduced folate carrier-1 80G>A polymorphism affects methotrexate treatment outcome in rheumatoid arthritis. Pharmacogenomics J. 2007;7(6):404-7.
Drozdzik, M., Rudas, T., Pawlik, A., Gornik, W., Kurzawski, M., & Herczynska, M. (2007). Reduced folate carrier-1 80G>A polymorphism affects methotrexate treatment outcome in rheumatoid arthritis. The Pharmacogenomics Journal, 7(6), pp. 404-7.
Drozdzik M, et al. Reduced Folate Carrier-1 80G>A Polymorphism Affects Methotrexate Treatment Outcome in Rheumatoid Arthritis. Pharmacogenomics J. 2007;7(6):404-7. PubMed PMID: 17325736.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reduced folate carrier-1 80G>A polymorphism affects methotrexate treatment outcome in rheumatoid arthritis. AU - Drozdzik,M, AU - Rudas,T, AU - Pawlik,A, AU - Gornik,W, AU - Kurzawski,M, AU - Herczynska,M, Y1 - 2007/02/27/ PY - 2007/2/28/pubmed PY - 2008/1/9/medline PY - 2007/2/28/entrez SP - 404 EP - 7 JF - The pharmacogenomics journal JO - Pharmacogenomics J. VL - 7 IS - 6 N2 - The folate antagonist methotrexate (MTX) is a drug currently used in the treatment of rheumatoid arthritis (RA). MTX enters the cells through the reduced folate carrier (RFC-1) and is activated to polyglutamates. Previous studies have shown that RFC-1 expression may influence the efficacy of therapy with MTX. The studies suggest that G80A polymorphism in RFC-1 is associated with altered folate/antifolate levels and the subjects carrying homozygous mutant 80AA genotype tend to have higher plasma folate and MTX concentrations and higher erythrocyte polyglutamate levels compared with those with the wild type or heterozygous genotype. It is possible that this polymorphism might influence MTX treatment outcome in patients with RA. In the present study, we examined the association between RFC-1 G80A polymorphism and treatment outcome in patients with RA administered MTX. The study was carried out on 174 patients diagnosed with RA treated with MTX (7.5-15.0 mg weekly) plus low doses of methylprednisone. The RFC-1 80G>A polymorphism (resulting in a histidine-to-arginine substitution at codon 27 of RFC-1) was detected using a polymerase chain reaction-restriction fragment length polymorphism method. The probability of remission of RA symptoms was 3.32-fold higher in carriers of 80AA genotype as compared with patients with 80GG genotype (P=0.021, OR=3.32, 95% CI: 1.26-8.79). The frequency of A allele among MTX responders was 62.1, compared to 47.8% in a group of poor MTX responders (P=0.013, OR=1.78, 95% CI: 1.13-2.81). Moreover, the increase of aminotransferase activity was noted more frequently in carriers of 80AA genotype. The present data suggest that evaluation of RFC-1 gene 80G>A polymorphism may be a useful tool to optimize MTX therapy in patients with RA. SN - 1470-269X UR - https://www.unboundmedicine.com/medline/citation/17325736/Reduced_folate_carrier_1_80G&gt L2 - http://dx.doi.org/10.1038/sj.tpj.6500438 DB - PRIME DP - Unbound Medicine ER -