title: Folate metabolic pathway single nucleotide polymorphisms: a predictive pharmacogenetic marker of methotrexate response in Indian (Asian) patients with rheumatoid arthritis.
abstract: OBJECTIVE
  We evaluated the pharmacogenetic influence of genetic polymorphisms in folate pathway genes in Indian rheumatoid arthritis patients receiving methotrexate (MTX).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Interdisciplinary School of Health Sciences, University of Pune, Pune 411007, India.|Department of Immunology & Division of Rheumatology, Mayo Clinic, Rochester, MN 55901, USA.
authors.forename: Yogita
authors.initials: Y
authors.lastname: Ghodke-Puranik
authors.affiliation: Interdisciplinary School of Health Sciences, University of Pune, Pune 411007, India.|Center for Aging, Mayo Clinic, Rochester, MN 55901, USA.
authors.forename: Amrutesh S
authors.initials: AS
authors.lastname: Puranik
authors.affiliation: Department of Biotechnology, Sinhgad College of Engineering, Pune 411041, India.|School of Anatomy, Physiology & Human Biology, University of Western Australia, Australia.
authors.forename: Pooja
authors.initials: P
authors.lastname: Shintre
authors.affiliation: Department of Biotechnology, Sinhgad College of Engineering, Pune 411041, India.
authors.forename: Kalpana
authors.initials: K
authors.lastname: Joshi
authors.affiliation: Interdisciplinary School of Health Sciences, University of Pune, Pune 411007, India.
authors.forename: Bhushan
authors.initials: B
authors.lastname: Patwardhan
authors.affiliation: University of Florida, Gainesville, FL 32610, USA.
authors.forename: Jatinder
authors.initials: J
authors.lastname: Lamba
authors.affiliation: Department of Immunology & Division of Rheumatology, Mayo Clinic, Rochester, MN 55901, USA.
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Niewold
authors.affiliation: Centre for Rheumatic Diseases, Pune 411001, India.
authors.forename: Arvind
authors.initials: A
authors.lastname: Chopra
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism; D044466:Asian People; D003430:Cross-Sectional Studies; D005260:Female; D005492:Folic Acid / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008727:Methotrexate / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012306:Risk
chemical_list: D018501:Antirheumatic Agents; D005492:Folic Acid; D008727:Methotrexate
keywords: Indians; folate metabolism; homocysteine; methotrexate; pharmacogenomics; pharmacokinetics