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Genetic Polymorphisms in Metabolic and Cellular Transport Pathway of Methotrexate Impact Clinical Outcome of Methotrexate Monotherapy in Japanese Patients with Rheumatoid Arthritis
- Source :
- Drug Metabolism and Pharmacokinetics. 27:192-199
- Publication Year :
- 2012
- Publisher :
- Japanese Society for the Study of Xenobiotics, 2012.
-
Abstract
- The aim of this study was to investigate the impact of genetic polymorphisms in the metabolic and cellular transport pathway of methotrexate (MTX) on the clinical outcome of MTX monotherapy in Japanese rheumatoid arthritis (RA) patients. Fifty-five patients were treated with MTX monotherapy at a dose of 4-10 mg/week. The total concentration of MTX-polyglutamates (MTX-PGs) was measured at steady-state in red blood cells (RBCs) by high performance liquid chromatography. The genotype at 16 polymorphic sites in 11 genes (ABCB1, ABCG2, ABCC2, RFC1, PCFT, SLCO1B1, MTHFR, GGH, ATIC, MTR, and MTRR) was analyzed. No significant association between the total concentration of MTX-PGs in RBCs and clinical outcome was found. However, patients with the ABCB1 3435TT genotype had a significantly lower mean disease activity score (DAS) 28 than did patients with the ABCB1 3435CC genotype (p = 0.02). Similarly, patients with the ABCB1 2677AA/AT/TT genotypes had a significantly lower mean DAS28 than did patients with the ABCB1 2677GG/GA/GT genotypes (p = 0.04). The patients with the MTHFR 1298AA genotype had a significantly lower mean DAS28 than those with the MTHFR 1298AC/CC genotypes (p = 0.04). In conclusion, the ABCB1 3435C>T, ABCB1 2677G>A/T, and MTHFR 1298A>C polymorphisms influenced the efficacy of MTX monotherapy.
- Subjects :
- Adult
Male
musculoskeletal diseases
medicine.medical_specialty
ATP Binding Cassette Transporter, Subfamily B
Biological Transport, Active
Pharmaceutical Science
Arthritis
Pharmacology
Gastroenterology
Arthritis, Rheumatoid
Asian People
Internal medicine
Genotype
medicine
Humans
Pharmacology (medical)
ATP Binding Cassette Transporter, Subfamily B, Member 1
skin and connective tissue diseases
Methylenetetrahydrofolate Reductase (NADPH2)
Aged
Retrospective Studies
Aged, 80 and over
Polymorphism, Genetic
biology
business.industry
Middle Aged
medicine.disease
MTRR
Multidrug Resistance-Associated Protein 2
Methotrexate
Treatment Outcome
Methylenetetrahydrofolate reductase
Rheumatoid arthritis
biology.protein
Female
SLCO1B1
business
Pharmacogenetics
medicine.drug
Subjects
Details
- ISSN :
- 13474367
- Volume :
- 27
- Database :
- OpenAIRE
- Journal :
- Drug Metabolism and Pharmacokinetics
- Accession number :
- edsair.doi.dedup.....b0d999282d52a593397936b3273cba15