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

被引：45
|
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
收藏
页码：2019 / 2034
页数：16
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