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

被引：47

作者：

Ghodke-Puranik, Yogita ^{[1
,2
,3
]}

Puranik, Amrutesh S. ^{[1
,4
]}

Shintre, Pooja ^{[5
,6
]}

Joshi, Kalpana ^{[5
]}

Patwardhan, Bhushan ^{[1
]}

Lamba, Jatinder ^{[7
]}

Niewold, Timothy B. ^{[2
,3
]}

Chopra, Arvind ^{[8
]}

机构：

[1] Univ Pune, Interdisciplinary Sch Hlth Sci, Pune 411007, Maharashtra, India

[2] Mayo Clin, Dept Immunol, Rochester, MN 55901 USA

[3] Mayo Clin, Div Rheumatol, Rochester, MN 55901 USA

[4] Mayo Clin, Ctr Aging, Rochester, MN 55901 USA

[5] Sinhgad Coll Engn, Dept Biotechnol, Pune 411041, Maharashtra, India

[6] Univ Western Australia, Sch Anat Physiol & Human Biol, Nedlands, WA 6009, Australia

[7] Univ Florida, Gainesville, FL 32610 USA

[8] Ctr Rheumat Dis, Pune 411001, Maharashtra, India

来源：

PHARMACOGENOMICS | 2015年 / 16卷 / 18期

关键词：

folate metabolism; homocysteine; Indians; methotrexate; pharmacogenomics; pharmacokinetics; THYMIDYLATE-SYNTHASE; GENETIC POLYMORPHISMS; LIQUID-CHROMATOGRAPHY; FLUORESCENCE DETECTION; COMMON POLYMORPHISMS; POLYGLUTAMATE LEVELS; JAPANESE PATIENTS; REDUCTASE GENES; DOUBLE-BLIND; EFFICACY;

D O I：

10.2217/pgs.15.145

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页码：2019 / 2034

页数：16

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