Yogita Ghodke-Puranik1,2, Amrutesh S Puranik1,3, Pooja Shintre4,5, Kalpana Joshi4, Bhushan Patwardhan1, Jatinder Lamba6, Timothy B Niewold2, Arvind Chopra7. 1. Interdisciplinary School of Health Sciences, University of Pune, Pune 411007, India. 2. Department of Immunology & Division of Rheumatology, Mayo Clinic, Rochester, MN 55901, USA. 3. Center for Aging, Mayo Clinic, Rochester, MN 55901, USA. 4. Department of Biotechnology, Sinhgad College of Engineering, Pune 411041, India. 5. School of Anatomy, Physiology & Human Biology, University of Western Australia, Australia. 6. University of Florida, Gainesville, FL 32610, USA. 7. Centre for Rheumatic Diseases, Pune 411001, India.
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.
AIM: We evaluated the pharmacogenetic influence of genetic polymorphisms in folate pathway genes in Indian rheumatoid arthritispatients 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 RApatients. 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 RApatients. A toxicogenetic index could identify patients who develop adverse events to MTX.
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