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

doi:10.2217/pgs.15.145

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

Rheumatology

Research output: Contribution to journal › Article › peer-review

33 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 language	English (US)
Pages (from-to)	2019-2034
Number of pages	16
Journal	Pharmacogenomics
Volume	16
Issue number	18
DOIs	https://doi.org/10.2217/pgs.15.145
State	Published - Dec 2015

Keywords

Indians
folate metabolism
homocysteine
methotrexate
pharmacogenomics
pharmacokinetics

ASJC Scopus subject areas

Molecular Medicine
Genetics
Pharmacology

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Folate metabolic pathway single nucleotide polymorphisms: A predictive pharmacogenetic marker of methotrexate response in Indian (Asian) patients with rheumatoid arthritis. / Ghodke-Puranik, Yogita; Puranik, Amrutesh S.; Shintre, Pooja et al.
In: Pharmacogenomics, Vol. 16, No. 18, 12.2015, p. 2019-2034.

Research output: Contribution to journal › Article › peer-review

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

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.",

keywords = "Indians, folate metabolism, homocysteine, methotrexate, pharmacogenomics, pharmacokinetics",

author = "Yogita Ghodke-Puranik and Puranik, {Amrutesh S.} and Pooja Shintre and Kalpana Joshi and Bhushan Patwardhan and Jatinder Lamba and Niewold, {Timothy B.} and Arvind Chopra",

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T2 - A predictive pharmacogenetic marker of methotrexate response in Indian (Asian) patients with rheumatoid arthritis

AU - Ghodke-Puranik, Yogita

AU - Puranik, Amrutesh S.

AU - Shintre, Pooja

AU - Joshi, Kalpana

AU - Patwardhan, Bhushan

AU - Lamba, Jatinder

AU - Niewold, Timothy B.

AU - Chopra, Arvind

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N2 - 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.

AB - 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.

KW - Indians

KW - folate metabolism

KW - homocysteine

KW - methotrexate

KW - pharmacogenomics

KW - pharmacokinetics

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

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ASJC Scopus subject areas

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