Polymorphisms in genes involved in the mechanism of action of methotrexate: Are they associated with outcome in rheumatoid arthritis patients?

Juliana Salazar; Patricia Moya; Albert Altés; César Díaz-Torné; Jordi Casademont; Dacia Cerdà-Gabaroi; Hèctor Corominas; Montserrat Baiget

doi:10.2217/pgs.14.67

Polymorphisms in genes involved in the mechanism of action of methotrexate: Are they associated with outcome in rheumatoid arthritis patients?

Juliana Salazar, Patricia Moya, Albert Altés, César Díaz-Torné, Jordi Casademont, Dacia Cerdà-Gabaroi, Hèctor Corominas, Montserrat Baiget

Department of Medicine

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

37 Citations (Scopus)

Abstract

Background: Methotrexate (MTX) is the first-line treatment option for newly diagnosed rheumatoid arthritis (RA) patients. However, 50-70% of the patients respond to treatment and 30% suffer toxicity. Aim: To identify pharmacogenetic markers of outcome in RA patients treated with MTX. Patients & methods: We analyzed 27 genetic variants in DHFR, TYMS, MTHFR, ATIC and CCND1 genes. Results: We included 124 RA patients treated with MTX monotherapy. In multivariate analyses two variants in the MTHFR gene were associated with response, rs17421511 (p = 0.024) and rs1476413 (p = 0.0086), as well as one in the DHFR gene, rs1643650 (p = 0.026). The ATIC rs16853826 variant was associated with toxicity (p = 0.039). Conclusion: MTHFR, DHFR and ATIC genetic variants can be considered as pharmacogenetic markers of outcome in RA patients under MTX monotherapy. © 2014 Future Medicine Ltd.

Original language	English
Pages (from-to)	1079-1090
Journal	Pharmacogenomics
Volume	15
Issue number	8
DOIs	https://doi.org/10.2217/pgs.14.67
Publication status	Published - 1 Jan 2014

Keywords

5,10-methylenetetrahydrofolate reductase
5-aminoimidazole-4-carboxamide ribonucleotide transformylase
ATIC
DHFR
dihydrofolate reductase
methotrexate
MTHFR
rheumatoid arthritis

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10.2217/pgs.14.67

Cite this

@article{34e6421ee34e425eafc1422720fdf1d7,

title = "Polymorphisms in genes involved in the mechanism of action of methotrexate: Are they associated with outcome in rheumatoid arthritis patients?",

abstract = "Background: Methotrexate (MTX) is the first-line treatment option for newly diagnosed rheumatoid arthritis (RA) patients. However, 50-70% of the patients respond to treatment and 30% suffer toxicity. Aim: To identify pharmacogenetic markers of outcome in RA patients treated with MTX. Patients & methods: We analyzed 27 genetic variants in DHFR, TYMS, MTHFR, ATIC and CCND1 genes. Results: We included 124 RA patients treated with MTX monotherapy. In multivariate analyses two variants in the MTHFR gene were associated with response, rs17421511 (p = 0.024) and rs1476413 (p = 0.0086), as well as one in the DHFR gene, rs1643650 (p = 0.026). The ATIC rs16853826 variant was associated with toxicity (p = 0.039). Conclusion: MTHFR, DHFR and ATIC genetic variants can be considered as pharmacogenetic markers of outcome in RA patients under MTX monotherapy. {\textcopyright} 2014 Future Medicine Ltd.",

keywords = "5,10-methylenetetrahydrofolate reductase, 5-aminoimidazole-4-carboxamide ribonucleotide transformylase, ATIC, DHFR, dihydrofolate reductase, methotrexate, MTHFR, rheumatoid arthritis",

author = "Juliana Salazar and Patricia Moya and Albert Alt{\'e}s and C{\'e}sar D{\'i}az-Torn{\'e} and Jordi Casademont and Dacia Cerd{\`a}-Gabaroi and H{\`e}ctor Corominas and Montserrat Baiget",

year = "2014",

month = jan,

day = "1",

doi = "10.2217/pgs.14.67",

language = "English",

volume = "15",

pages = "1079--1090",

journal = "Pharmacogenomics",

issn = "1462-2416",