Methotrexate pharmacokinetic genetic variants are associated with outcome in rheumatoid arthritis patients

Patricia Moya; Juliana Salazar; María Jesús Arranz; César Díaz-Torné; Elisabeth Del Río; Jordi Casademont; Hèctor Corominas; Montserrat Baiget

doi:10.2217/pgs.15.150

Methotrexate pharmacokinetic genetic variants are associated with outcome in rheumatoid arthritis patients

Patricia Moya, Juliana Salazar, María Jesús Arranz, César Díaz-Torné, Elisabeth Del Río, Jordi Casademont, Hèctor Corominas, Montserrat Baiget

Department of Medicine

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

34 Citations (Scopus)

Abstract

Background: Methotrexate (MTX) is the most used drug for the treatment of rheumatoid arthritis (RA) although outcome differs among patients. Aim: To evaluate whether polymorphisms in pharmacokinetic genes are associated with outcome in RA patients receiving MTX. Patients & methods: We analyzed 28 SNPs in SLC19A1/RFC1, ABCB1, FPGS and GGH genes. Results: We studied 194 RA patients receiving MTX monotherapy. Two FPGS SNPs, rs10987742 and rs10106, were associated with response (p = 0.033 and p = 0.041, respectively). The FPGS rs10106 variant was also associated with MTX survival (p = 0.005) and toxicity (p = 0.021). Three ABCB1 SNPs, rs868755, rs10280623 and rs1858923, were associated with toxicity (p = 0.025, p = 0.048 and p = 0.031, respectively). Conclusion: FPGS and ABCB1 genetic variants can influence the outcome in RA patients receiving MTX monotherapy.

Original language	English
Pages (from-to)	11-25
Number of pages	16
Journal	Pharmacogenomics
Volume	17
Issue number	1
DOIs	https://doi.org/10.2217/pgs.15.150
Publication status	Published - Jan 2016

Keywords

ABCB1
FPGS
GGH
methotrexate
pharmacogenetics
rheumatoid arthritis
SLC19A1/RFC1

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title = "Methotrexate pharmacokinetic genetic variants are associated with outcome in rheumatoid arthritis patients",

abstract = "Background: Methotrexate (MTX) is the most used drug for the treatment of rheumatoid arthritis (RA) although outcome differs among patients. Aim: To evaluate whether polymorphisms in pharmacokinetic genes are associated with outcome in RA patients receiving MTX. Patients & methods: We analyzed 28 SNPs in SLC19A1/RFC1, ABCB1, FPGS and GGH genes. Results: We studied 194 RA patients receiving MTX monotherapy. Two FPGS SNPs, rs10987742 and rs10106, were associated with response (p = 0.033 and p = 0.041, respectively). The FPGS rs10106 variant was also associated with MTX survival (p = 0.005) and toxicity (p = 0.021). Three ABCB1 SNPs, rs868755, rs10280623 and rs1858923, were associated with toxicity (p = 0.025, p = 0.048 and p = 0.031, respectively). Conclusion: FPGS and ABCB1 genetic variants can influence the outcome in RA patients receiving MTX monotherapy.",

keywords = "ABCB1, FPGS, GGH, methotrexate, pharmacogenetics, rheumatoid arthritis, SLC19A1/RFC1",

author = "Patricia Moya and Juliana Salazar and Arranz, {Mar{\'i}a Jes{\'u}s} and C{\'e}sar D{\'i}az-Torn{\'e} and {Del R{\'i}o}, Elisabeth and Jordi Casademont and H{\`e}ctor Corominas and Montserrat Baiget",

year = "2016",

month = jan,

doi = "10.2217/pgs.15.150",

language = "English",

volume = "17",

pages = "11--25",

journal = "Pharmacogenomics",

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publisher = "Future Medicine Ltd.",

number = "1",

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TY - JOUR

T1 - Methotrexate pharmacokinetic genetic variants are associated with outcome in rheumatoid arthritis patients

AU - Moya, Patricia

AU - Salazar, Juliana

AU - Arranz, María Jesús

AU - Díaz-Torné, César

AU - Del Río, Elisabeth

AU - Casademont, Jordi

AU - Corominas, Hèctor

AU - Baiget, Montserrat

PY - 2016/1

Y1 - 2016/1

N2 - Background: Methotrexate (MTX) is the most used drug for the treatment of rheumatoid arthritis (RA) although outcome differs among patients. Aim: To evaluate whether polymorphisms in pharmacokinetic genes are associated with outcome in RA patients receiving MTX. Patients & methods: We analyzed 28 SNPs in SLC19A1/RFC1, ABCB1, FPGS and GGH genes. Results: We studied 194 RA patients receiving MTX monotherapy. Two FPGS SNPs, rs10987742 and rs10106, were associated with response (p = 0.033 and p = 0.041, respectively). The FPGS rs10106 variant was also associated with MTX survival (p = 0.005) and toxicity (p = 0.021). Three ABCB1 SNPs, rs868755, rs10280623 and rs1858923, were associated with toxicity (p = 0.025, p = 0.048 and p = 0.031, respectively). Conclusion: FPGS and ABCB1 genetic variants can influence the outcome in RA patients receiving MTX monotherapy.

AB - Background: Methotrexate (MTX) is the most used drug for the treatment of rheumatoid arthritis (RA) although outcome differs among patients. Aim: To evaluate whether polymorphisms in pharmacokinetic genes are associated with outcome in RA patients receiving MTX. Patients & methods: We analyzed 28 SNPs in SLC19A1/RFC1, ABCB1, FPGS and GGH genes. Results: We studied 194 RA patients receiving MTX monotherapy. Two FPGS SNPs, rs10987742 and rs10106, were associated with response (p = 0.033 and p = 0.041, respectively). The FPGS rs10106 variant was also associated with MTX survival (p = 0.005) and toxicity (p = 0.021). Three ABCB1 SNPs, rs868755, rs10280623 and rs1858923, were associated with toxicity (p = 0.025, p = 0.048 and p = 0.031, respectively). Conclusion: FPGS and ABCB1 genetic variants can influence the outcome in RA patients receiving MTX monotherapy.

KW - ABCB1

KW - FPGS

KW - GGH

KW - methotrexate

KW - pharmacogenetics

KW - rheumatoid arthritis

KW - SLC19A1/RFC1

UR - http://europepmc.org/abstract/med/26652611

U2 - 10.2217/pgs.15.150

DO - 10.2217/pgs.15.150

M3 - Article

C2 - 26652611

SN - 1462-2416

VL - 17

SP - 11

EP - 25

JO - Pharmacogenomics

JF - Pharmacogenomics

IS - 1

ER -

Methotrexate pharmacokinetic genetic variants are associated with outcome in rheumatoid arthritis patients

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