Abstract
Aim: We evaluated the pharmacogenetic influence of genetic polymorphisms in folate pathway genes in Indian rheumatoid arthritis patients receiving methotrexate (MTX). Patients & methods: Twelve polymorphisms within nine folate pathway genes were analyzed for association with MTX response in 322 Indian rheumatoid arthritis (RA) patients and MTX pharmacokinetics in 94 RA patients. Results: Polymorphisms in GGH, SHMT1 and TS were associated with MTX-related adverse events while SNPs in MTHFR and RFC1/SLC19A1 were associated with MTX efficacy. TS5′UTR and SHMT1 polymorphisms were associated with higher plasma levels of MTX. Conclusion: Polymorphisms in folate-MTX pathway genes contribute to MTX response and affect MTX concentrations in Indian RA patients. A toxicogenetic index could identify patients who develop adverse events to MTX.
Original language | English (US) |
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Pages (from-to) | 2019-2034 |
Number of pages | 16 |
Journal | Pharmacogenomics |
Volume | 16 |
Issue number | 18 |
DOIs | |
State | Published - Dec 2015 |
Keywords
- Indians
- folate metabolism
- homocysteine
- methotrexate
- pharmacogenomics
- pharmacokinetics
ASJC Scopus subject areas
- Molecular Medicine
- Genetics
- Pharmacology