Genetic variants associated with methotrexate efficacy and toxicity in early rheumatoid arthritis: Results from the treatment of early aggressive rheumatoid arthritis trial

Pharmacogenomics Journal

Volumn 14, Issue 1, 2014, Pages 48-53

  Aslibekyan, S ^a   Brown, E E ^a   Reynolds, R J ^b   Redden, D T ^a   Morgan, S ^b   Baggott, J E ^a   Sha, J ^a   Moreland, L W ^c   O'Dell, J R ^d   Curtis, J R ^b   Mikuls, T R ^d   Bridges, S L ^b   Arnett, D K ^a  

^a UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^b University of Alabama at Birmingham   (United States)

^c UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^d UNIVERSITY OF NEBRASKA MEDICAL CENTER   (United States)

Author keywords

methotrexate; pharmacogenetics; rheumatoid arthritis

Indexed keywords

CHONDROITIN; GENOMIC DNA; METHOTREXATE;

ALDH2 GENE; ARTICLE; CHST11 GENE; CLINICAL TRIAL (TOPIC); CYP20A1 GENE; DRUG EFFICACY; GENE; GENETIC ASSOCIATION; GENETIC VARIABILITY; HUMAN; INFECTION; MARKER GENE; OUTCOME ASSESSMENT; PHARMACOGENETICS; PRIORITY JOURNAL; RHEUMATOID ARTHRITIS; SLC22A2 GENE; SLC7A7 GENE; TREATMENT RESPONSE; UNSPECIFIED SIDE EFFECT;

ANTIRHEUMATIC AGENTS; ARTHRITIS, RHEUMATOID; BIOLOGICAL MARKERS; FEMALE; GENETIC VARIATION; HUMANS; MALE; METHOTREXATE; MIDDLE AGED; MULTIVARIATE ANALYSIS; RANDOMIZED CONTROLLED TRIALS AS TOPIC; REGRESSION ANALYSIS; SEVERITY OF ILLNESS INDEX; TIME FACTORS; TREATMENT OUTCOME;

EID: 84893640103     PISSN: 1470269X     EISSN: 14731150     Source Type: Journal    
DOI: 10.1038/tpj.2013.11     Document Type: Article

References (36)

1. Saag KG, Teng GG, Patkar NM, Anuntiyo J, Finney C, Curtis JR et al. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum 2008; 59: 762-784.
2. Smolen JS, Landewe R, Breedveld FC, Dougados M, Emery P, Gaujoux-Viala C et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis 2010; 69: 964-975.
3. Drouin J, Haraoui B. 3e Initiative Group. Predictors of clinical response and radiographic progression in patients with rheumatoid arthritis treated with methotrexate monotherapy. J Rheumatol 2010; 37: 1405-1410.
4. Saevarsdottir S, Wallin H, Seddighzadeh M, Ernestam S, Geborek P, Petersson IF et al. Predictors of response to methotrexate in early DMARD nave rheumatoid arthritis: results from the initial open-label phase of the SWEFOT trial. Ann Rheum Dis 2011; 70: 469-475.
5. Kremer JM. Methotrexate pharmacogenomics. Ann Rheum Dis 2006; 65: 1121-1123.
6. Dervieux T, Greenstein N, Kremer J. Pharmacogenomic and metabolic biomarkers in the folate pathway and their association with methotrexate effects during dosage escalation in rheumatoid arthritis. Nat Clin Pract Rheumatol 2007; 3: 256-257.
7. Criswell LA, Lum RF, Turner KN, Woehl B, Zhu Y, Wang J et al. The influence of genetic variation in the HLA-DRB1 and LTA-TNF regions on the response to treatment of early rheumatoid arthritis with methotrexate or etanercept. Arthritis Rheum 2004; 50: 2750-2756.
8. Sharma S, Das M, Kumar A, Marwaha V, Shankar S, Singh P et al. Purine biosynthetic pathway genes and methotrexate response in rheumatoid arthritis patients among north Indians. Pharmacogenet Genomics 2009; 19: 823-828.
9. Wessels JA, de Vries-Bouwstra JK, Heijmans BT, Slagboom PE, Goekoop-Ruiterman YP, Allaart CF et al. Efficacy and toxicity of methotrexate in early rheumatoid arthritis are associated with single-nucleotide polymorphisms in genes coding for folate pathway enzymes. Arthritis Rheum 2006; 54: 1087-1095.
10. Wessels JA, Kooloos WM, De Jonge R, De Vries-Bouwstra JK, Allaart CF, Linssen A et al. Relationship between genetic variants in the adenosine pathway and outcome of methotrexate treatment in patients with recent-onset rheumatoid arthritis. Arthritis Rheum 2006; 54: 2830-2839.
11. Breedveld FC, Weisman MH, Kavanaugh AF, Cohen SB, Pavelka K, van Vollenhoven R et al. The PREMIER study: a multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis Rheum 2006; 54: 26-37.
12. Moreland LW, ODell JR, Paulus HE, Curtis JR, Bathon JM, St Clair EW et al. A randomized comparative effectiveness study of oral triple therapy versus etanercept plus methotrexate in early, aggressive rheumatoid arthritis. Arthritis Rheum 2012; 64: 2824-2835.
13. Moreland LW, ODell JR, Paulus HE, Curtis JR, Bridges SL, Zhang X et al. TEAR- Treatment of early aggressive rheumatoid arthritis: a randomized, double-blind 2 year trial comparing immediate triple DMARD vs methotrexate and etanercept to step-up from initial methotrexate monotherapy. Arthritis Rheum 2009; 60: S707.
14. Moreland LW, ODell JR, Paulus HE, Curtis JR, Bathon JM, St Clair EW et al. Two-year radiographic results from the TEAR trial. Arthritis Rheum 2010; 62: S1368.
15. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988; 31: 315-324.
16. Prevoo ML, van t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995; 38: 44-48.
17. Burmeister JK, Sedova M, Shapero MH, Mansfield E. DMET microarray technology for pharmacogenomics-based personalized medicine. Methods Mol Biol 2010; 632: 99-124.
18. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D et al. PLINK: a toolset for whole-genome association and population-based linkage analysis. Am J Hum Genet 2007; 81: 559-575.
19. Draper N, Smith H. Applied Regression Analysis, 3rd edn. (Wiley: New York, NY, USA, 1998).
20. Tibshirani R. Regression shrinkage and selection via the lasso. J Royal Statist Soc B 1996; 58: 267-288.
21. Wu TT, Chen YF, Hastie T, Sobel E, Lange K. Genome-wide association analysis by lasso penalized logistic regression. Bioinformatics 2009; 25: 714-721.
22. Zhou H, Sehl ME, Sinsheimer JS, Lange K. Association screening of common and rare genetic variants by penalized regression. Bioinformatics 2010; 26: 2375-2382.
23. Lange K, Cantor R, Horvath S, Perola M, Sabatti C, Sinsheimer J et al. Mendel version 4.0: a complete package for the exact genetic analysis of discrete traits in pedigree and population data sets. Am J Hum Genet 2001; 69(Supplement): 504.
24. The R Core Group. R (Version 2.13.0). Available at http://CRAN.R-project. org/.
25. Baggott JE, Bridges SL, Morgan SL. Evidence for two phenotypes in the metabolism of methotrexate to 7-hydroxymethotrexate in patients with rheumatoid arthritis. Arthritis Rheum 2005; 52: 356-358.
26. Baggott JE, Morgan SL. Methotrexate catabolism to 7-hydroxymethotrexate in rheumatoid arthritis alters drug efficacy and retention and is reduced by folic acid supplementation. Arthritis Rheum 2009; 60: 2257-2261.
27. Moscow JA, Gong M, He R, Sgagias MK, Dixon KH, Anzick SL et al. Isolation of a gene encoding a human reduced folate carrier (RFC1) and analysis of its expression in transport-deficient, methotrexate-resistant human breast cancer cells. Cancer Res 1995; 55: 3790-3794.
28. Trevino LR, Shimasaki N, Yang W, Panetta JC, Cheng C, Pei D et al. Germline genetic variation in an organic anion transporter polypeptide associated with methotrexate pharmacokinetics and clinical effects. J Clin Oncol 2009; 27: 5972-5978.
29. Faganel Kotnik B, Grabnar I, Bohanec Grabar P, Dolzan V, Jazbec J. Association of genetic polymorphism in the folate metabolic pathway with methotrexate pharmacokinetics and toxicity in childhood acute lymphoblastic leukaemia and malignant lymphoma. Eur J Clin Pharmacol 2011; 67: 993-1006.
30. Dervieux T, Wessels JA, Kremer JM, Padyukov L, Seddighzadeh M, Saevarsdottir S et al. Patterns of interaction between genetic and nongenetic attributes and methotrexate efficacy in rheumatoid arthritis. Pharmacogenet Genomics 2012; 22: 1-9.
31. Wessels JA, van der Kooij SM, le Cessie S, Kievit W, Barerra P, Allaart CF et al. A clinical pharmacogenetic model to predict the efficacy of methotrexate monotherapy in recent-onset rheumatoid arthritis. Arthritis Rheum 2007; 56: 1765-1775.
32. Grabar PB, Logar D, Lestan B, Dolzan V. Genetic determinants of methotrexate toxicity in rheumatoid artritis patients: a study of polymorphisms affecting methotrexate transport and folate metabolism. Eur J Clin Pharmacol 2008; 64: 1057-1068.
33. Berkun Y, Levartovsky D, Rubinow A, Orbach H, Aamar S, Grenader T et al. Methotrexate related adverse effects in patients with rheumatoid arthritis are associated with the A1298C polymorphism of the MTHFR gene. Ann Rheum Dis 2004; 63: 227-231.
34. Falconer DS. Mackay TFC. Introduction to Quantitative Genetics. 4th edn (Pearson Education Limited: Essex, 1996).
35. Morgan SL, Baggott JE. Folate supplementation during methotrexate therapy for rheumatoid arthritis. Clin Exp Rheumatol 2010; 28: S102-S109.
36. Hughes LB, Beasley TM, Patel H, Tiwari HK, Morgan SL, Baggott JE et al. Racial or ethnic differences in allele frequencies of single-nucleotide polymorphisms in the methylenetetrahydrofolate reductase gene and their influence on response to methotrexate in rheumatoid arthritis. Ann Rheum Dis 2006; 65: 1213-1218.