Folate metabolic pathway single nucleotide polymorphisms: A predictive pharmacogenetic marker of methotrexate response in Indian (Asian) patients with rheumatoid arthritis

Yogita Ghodke-Puranik, Amrutesh S. Puranik, Pooja Shintre, Kalpana Joshi, Bhushan Patwardhan, Jatinder Lamba, Timothy B. Niewold, Arvind Chopra

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

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 languageEnglish (US)
Pages (from-to)2019-2034
Number of pages16
JournalPharmacogenomics
Volume16
Issue number18
DOIs
StatePublished - Dec 2015

Keywords

  • Indians
  • folate metabolism
  • homocysteine
  • methotrexate
  • pharmacogenomics
  • pharmacokinetics

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmacology

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