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

被引：0

作者：

Salazar, Juliana ^{[1
,2
]}

Moya, Patricia ^{[3
,4
]}

Altes, Albert ^{[5
]}

Diaz-Torne, Cesar ^{[3
]}

Casademont, Jordi ^{[3
]}

Cerda-Gabaroi, Dacia ^{[6
]}

Corominas, Hector ^{[6
]}

Baiget, Montserrat ^{[1
,2
]}

机构：

[1] Hosp Santa Creu & Sant Pau, Dept Genet, Barcelona 08025, Spain

[2] CIBERER, U705, Barcelona, Spain

[3] Hosp Santa Creu & Sant Pau, Internal Med Dept, Barcelona 08025, Spain

[4] Univ Autonoma Barcelona, E-08193 Barcelona, Spain

[5] Fundacio Althaia, Hematol Dept, Barcelona, Spain

[6] Hosp Moises Broggi, Rheumatol Dept, Barcelona, Spain

来源：

PHARMACOGENOMICS | 2014年 / 15卷 / 08期

关键词：

5-aminoimidazole-4-carboxamide ribonucleotide transformylase; 5,10-methylenetetrahydrofolate reductase; ATIC; DHFR; dihydrofolate reductase; methotrexate; MTHFR; rheumatoid arthritis; CLINICAL PHARMACOGENETIC MODEL; FUNCTIONAL-ANALYSIS; EFFICACY; RECOMMENDATIONS; MONOTHERAPY; MANAGEMENT; TOXICITY; PREDICT;

D O I：

10.2217/PGS.14.67

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页码：1079 / 1090

页数：12

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