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

ABSTRACT: We evaluated the pharmacogenetic influence of genetic polymorphisms in folate pathway genes in Indian rheumatoid arthritis patients receiving methotrexate (MTX).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.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.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.

SUBMITTER: Ghodke-Puranik Y

PROVIDER: S-EPMC4976849 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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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 Y Puranik Amrutesh S AS Shintre Pooja P Joshi Kalpana K Patwardhan Bhushan B Lamba Jatinder J Niewold Timothy B TB Chopra Arvind A

Pharmacogenomics 20151130 18

<h4>Aim</h4>We evaluated the pharmacogenetic influence of genetic polymorphisms in folate pathway genes in Indian rheumatoid arthritis patients receiving methotrexate (MTX).<h4>Patients & methods</h4>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.<h4>Results</h4>Polymorphisms in GGH, SHMT1 and TS were associated with MTX-related adverse events while S ...[more]

PMID: 26616421

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Project description:IntroductionLimited data are available to explain nonadherence to methotrexate (MTX) therapy in patients with rheumatoid arthritis (RA). Better understanding of patterns of MTX use and reasons for nonadherence may help identify patients who would benefit from alternative RA treatments and potentially aid in developing strategies to increase overall adherence. The purpose of this study was to assess patients' self-reported adherence to MTX and to identify reasons for nonadherence.MethodsPatient panel members in the US self-reporting a diagnosis of RA of ?3 months' and current MTX use of ?4 weeks' duration, with or without concomitant use of another RA prescription medication, participated in this cross-sectional, web-based survey.ResultsThe sample population (251 MTX monotherapy, 250 MTX combination therapy) was predominantly female, white, non-Hispanic, and educated; 48% were 18-44 years-old, 47% had medical comorbidities, 66% were first diagnosed with RA ?5 years earlier, 51% reported MTX use of <1 year, and 83% reported oral MTX use. Forty-two percent reported not taking MTX exactly as prescribed. Reasons for nonadherence included forgetting to take it (33%), not needing it when feeling well (24%), and concern about long-term safety (24%). Among nonadherent patients, 53% took smaller doses, 52% skipped doses, and 6% reported other nonprescribed ways of taking MTX. Younger age, male sex, and shorter duration of MTX use were associated with poorer self-reported adherence. Compared with monotherapy patients, combination therapy patients, particularly those taking ?2 other RA prescriptions, were less likely to report high adherence.ConclusionNearly half the sample reported poor MTX adherence because they forgot to take it, thought it was not needed when they felt well, or had long-term safety concerns. Patients taking ?2 other RA prescription medications were less likely to report good adherence. Reducing treatment burden without sacrificing efficacy may be a strategy worth evaluating.

Dataset Information

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

Publications

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

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