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

共 29 条

[1]

Albrecht K, 2010, CLIN EXP RHEUMATOL, V28, pS95

[2]

Aletaha D, 2005, CLIN EXP RHEUMATOL, V23, pS100

[3] The rheumatoid arthritis patient in the clinic: comparing more than 1300 consecutive DMARD courses [J].

Aletaha, D ;

Smolen, JS .

RHEUMATOLOGY, 2002, 41 (12) :1367-1374

[4] Annotation of functional variation in personal genomes using RegulomeDB [J].

Boyle, Alan P. ;

Hong, Eurie L. ;

Hariharan, Manoj ;

Cheng, Yong ;

Schaub, Marc A. ;

Kasowski, Maya ;

Karczewski, Konrad J. ;

Park, Julie ;

Hitz, Benjamin C. ;

Weng, Shuai ;

Cherry, J. Michael ;

Snyder, Michael .

GENOME RESEARCH, 2012, 22 (09) :1790-1797

[5] EULAR recommendations for the management of early arthritis: report of a task force of the European Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT) [J].

Combe, B. ;

Landewe, R. ;

Lukas, C. ;

Bolosiu, H. D. ;

Breedveld, F. ;

Dougados, M. ;

Emery, P. ;

Ferraccioli, G. ;

Hazes, J. M. W. ;

Klareskog, L. ;

Machold, K. ;

Martin-Mola, E. ;

Nielsen, H. ;

Silman, A. ;

Smolen, J. ;

Yazici, H. .

ANNALS OF THE RHEUMATIC DISEASES, 2007, 66 (01) :34-45

[6] THE ANTIINFLAMMATORY MECHANISM OF METHOTREXATE - INCREASED ADENOSINE RELEASE AT INFLAMED SITES DIMINISHES LEUKOCYTE ACCUMULATION IN AN IN-VIVO MODEL OF INFLAMMATION [J].

CRONSTEIN, BN ;

NAIME, D ;

OSTAD, E .

JOURNAL OF CLINICAL INVESTIGATION, 1993, 92 (06) :2675-2682

[7] DNA variants in the dihydrofolate reductase gene and outcome in childhood ALL [J].

Dulucq, Stephanie ;

St-Onge, Genevieve ;

Gagne, Vincent ;

Ansari, Marc ;

Sinnett, Daniel ;

Labuda, Damian ;

Moghrabi, Albert ;

Krajinovic, Maja .

BLOOD, 2008, 111 (07) :3692-3700

[8]

Fransen J, 2005, CLIN EXP RHEUMATOL, V23, pS93

[9]

Fransen J, 2012, PHARMACOGENOMICS, V13, P1087, DOI [10.2217/PGS.12.83, 10.2217/pgs.12.83]

[10]

GALIVAN J, 1980, MOL PHARMACOL, V17, P105

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