Advanced search
Publication Cover
Pharmacogenomics Volume 15, 2014 - Issue 4
Submit an article Journal homepage
435
Views
2
CrossRef citations to date
0
Altmetric
Review

Pharmacogenetics and Pharmacogenomics for Rheumatoid Arthritis Responsiveness to Methotrexate Treatment: The 2013 Update

Hong Zhu1 Center for Genetic Epidemiology & Genomics, School of Public Health, Soochow University, Suzhou, Jiangsu 215123, PRChinaView further author information
,
Fei-Yan Deng1 Center for Genetic Epidemiology & Genomics, School of Public Health, Soochow University, Suzhou, Jiangsu 215123, PRChinaView further author information
,
Xing-Bo Mo1 Center for Genetic Epidemiology & Genomics, School of Public Health, Soochow University, Suzhou, Jiangsu 215123, PRChinaView further author information
,
Ying-Hua Qiu1 Center for Genetic Epidemiology & Genomics, School of Public Health, Soochow University, Suzhou, Jiangsu 215123, PRChinaView further author information
&
Shu-Feng Lei1 Center for Genetic Epidemiology & Genomics, School of Public Health, Soochow University, Suzhou, Jiangsu 215123, PRChinaCorrespondence[email protected]
View further author information
Pages 551-566 | Published online: 13 Mar 2014

References

  • Bansard C , LequerreT, DaveauM et al. Can rheumatoid arthritis responsiveness to methotrexate and biologics be predicted? Rheumatology (Oxford) 48(9) , 1021–1028 (2009).
  • Ranganathan P . An update on methotrexate pharmacogenetics in rheumatoid arthritis. Pharmacogenomics9(4) , 439–451 (2008).
  • Stamp LK , RobertsRL. Effect of genetic polymorphisms in the folate pathway on methotrexate therapy in rheumatic diseases. Pharmacogenomics12(10) , 1449–1463 (2011).
  • Wang Z , ZhouQ, KruhGD, GalloJM. Dose-dependent disposition of methotrexate in Abcc2 and Abcc3 gene knockout murine models. Drug Metab. Dispos.39(11) , 2155–2161 (2011).
  • Vlaming ML , van Esch A, van de Steeg E et al. Impact of abcc2 [multidrug resistance-associated protein (MRP) 2], abcc3 (MRP3), and abcg2 (breast cancer resistance protein) on the oral pharmacokinetics of methotrexate and its main metabolite 7-hydroxymethotrexate. Drug Metab. Dispos.39(8) , 1338–1344 (2011).
  • Blits M , JansenG, VosslamberS, AssarafYG, VerweijCL. Gene expression profiling of folate pathway related genes in methotrexate naive-and methotrexate-treated rheumatoid arthritis patients. Ann. Rheum. Dis.71 , A53–A53 (2012).
  • De Rotte MC , BulatovicM, HeijstekMW et al. ABCB1 and ABCC3 gene polymorphisms are associated with first-year response to methotrexate in juvenile idiopathic arthritis. J. Rheumatol.39(10) , 2032–2040 (2012).
  • Kato T , HamadaA, MoriS, SaitoH. Genetic polymorphisms in metabolic and cellular transport pathway of methotrexate impact clinical outcome of methotrexate monotherapy in Japanese patients with rheumatoid arthritis. Drug Metab. Pharmacokinet.27(2) , 192–199 (2012).
  • Plaza-Plaza JC , AguileraM, Canadas-GarreM et al. Pharmacogenetic polymorphisms contributing to toxicity induced by methotrexate in the southern Spanish population with rheumatoid arthritis. OMICS 16(11) , 589–595 (2012).
  • Kooloos WM , WesselsJA, van der Straaten T, Allaart CF, Huizinga TW, Guchelaar HJ. Functional polymorphisms and methotrexate treatment outcome in recent-onset rheumatoid arthritis. Pharmacogenomics11(2) , 163–175 (2010).
  • Hayashi H , TazoeY, TsuboiS et al. A single nucleotide polymorphism of reduced folate carrier 1 predicts methotrexate efficacy in Japanese patients with rheumatoid arthritis. Drug Metab. Pharmacokinet. 28(2) , 164–168 (2013).
  • Yanagimachi M , NarutoT, HaraT et al. Influence of polymorphisms within the methotrexate pathway genes on the toxicity and efficacy of methotrexate in patients with juvenile idiopathic arthritis. Br. J. Clin. Pharmacol. 71(2) , 237–243 (2011).
  • Kung TN , DennisJ, MaY et al. RFC-1 80G>A is a genetic determinant of methotrexate efficacy in rheumatoid arthritis: a HuGE review and meta-analysis of observational studies. Arthritis Rheum. doi:10.1002/art.38331 (2013) (Epub ahead of print).
  • Bohanec Grabar P , Leandro-GarciaLJ, Inglada-PerezL, LogarD, Rodriguez-AntonaC, DolzanV. Genetic variation in the SLC19A1 gene and methotrexate toxicity in rheumatoid arthritis patients. Pharmacogenomics13(14) , 1583–1594 (2012).
  • Lima A , BernardesM, SousaH et al. SLC19A1 80G allele as a biomarker of methotrexate-related gastrointestinal toxicity in Portuguese rheumatoid arthritis patients. Pharmacogenomics doi:10.2217/PGS.13.244 (2013) (Epub ahead of print).
  • Owen SA , HiderSL, MartinP, BruceIN, BartonA, ThomsonW. Genetic polymorphisms in key methotrexate pathway genes are associated with response to treatment in rheumatoid arthritis patients. Pharmacogenomics J.13(3) , 227–234 (2013).
  • Moncrieffe H , HinksA, UrsuS et al. Generation of novel pharmacogenomic candidates in response to methotrexate in juvenile idiopathic arthritis: correlation between gene expression and genotype. Pharmacogenet. Genomics 20(11) , 665–676 (2010).
  • Jekic B , LukovicL, BunjevackiV et al. Association of the TYMS 3G/3G genotype with poor response and GGH 354GG genotype with the bone marrow toxicity of the methotrexate in RA patients. Eur. J. Clin. Pharmacol. 69(3) , 377–383 (2013).
  • Sharma S , DasM, KumarA et al. Purine biosynthetic pathway genes and methotrexate response in rheumatoid arthritis patients among north Indians. Pharmacogenet. Genomics 19(10) , 823–828 (2009).
  • Hayashi H , FujimakiC, DaimonT, TsuboiS, MatsuyamaT, ItohK. Genetic polymorphisms in folate pathway enzymes as a possible marker for predicting the outcome of methotrexate therapy in Japanese patients with rheumatoid arthritis. J. Clin. Pharm. Ther.34(3) , 355–361 (2009).
  • Wessels JA , de Vries-Bouwstra JK, Heijmans BT 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.54(4) , 1087–1095 (2006).
  • Milic V , JekicB, LukovicL et al. Association of dihydrofolate reductase (DHFR) -317AA genotype with poor response to methotrexate in patients with rheumatoid arthritis. Clin. Exp. Rheumatol. 30(2) , 178–183 (2012).
  • James HM , GillisD, HissariaP et al. Common polymorphisms in the folate pathway predict efficacy of combination regimens containing methotrexate and sulfasalazine in early rheumatoid arthritis. J. Rheumatol. 35(4) , 562–571 (2008).
  • Lee YC , CuiJ, CostenbaderKH, ShadickNA, WeinblattME, KarlsonEW. Investigation of candidate polymorphisms and disease activity in rheumatoid arthritis patients on methotrexate. Rheumatology (Oxford)48(6) , 613–617 (2009).
  • Iannaccone CK , LeeYC, CuiJ et al. Using genetic and clinical data to understand response to disease-modifying anti-rheumatic drug therapy: data from the Brigham and Women‘s Hospital Rheumatoid Arthritis Sequential Study. Rheumatology (Oxford) 50(1) , 40–46 (2011).
  • Hinks A , MoncrieffeH, MartinP et al. Association of the 5-aminoimidazole-4-carboxamide ribonucleotide transformylase gene with response to methotrexate in juvenile idiopathic arthritis. Ann. Rheum. Dis. 70(8) , 1395–1400 (2011).
  • Oliveira RD , FontanaV, JuntaCM et al. Differential gene expression profiles may differentiate responder and nonresponder patients with rheumatoid arthritis for methotrexate (MTX) monotherapy and mtx plus tumor necrosis factor inhibitor combined therapy. J. Rheumatol. 39(8) , 1524–1532 (2012).
  • Stamp LK , ChapmanPT, O‘DonnellJL et al. Polymorphisms within the folate pathway predict folate concentrations but are not associated with disease activity in rheumatoid arthritis patients on methotrexate. Pharmacogenet. Genomics 20(6) , 367–376 (2010).
  • Owen SA , LuntM, BowesJ et al. MTHFR gene polymorphisms and outcome of methotrexate treatment in patients with rheumatoid arthritis: analysis of key polymorphisms and meta-analysis of C677T and A1298C polymorphisms. Pharmacogenomics J.13(2) , 137–147 (2013).
  • Taraborelli M , AndreoliL, ArchettiS, FerrariM, CattaneoR, TincaniA. Methylenetetrahydrofolate reductase polymorphisms and methotrexate: no association with response to therapy nor with drug-related adverse events in an Italian population of rheumatic patients. Clin. Exp. Rheumatol.27(3) , 499–502 (2009).
  • Xiao H , XuJ, ZhouX et al. Associations between the genetic polymorphisms of MTHFR and outcomes of methotrexate treatment in rheumatoid arthritis. Clin. Exp. Rheumatol. 28(5) , 728–733 (2010).
  • Tukova J , ChladekJ, HrochM, NemcovaD, HozaJ, DolezalovaP. 677TT genotype is associated with elevated risk of methotrexate (MTX) toxicity in juvenile idiopathic arthritis: treatment outcome, erythrocyte concentrations of MTX and folates, and MTHFR polymorphisms. J. Rheumatol.37(10) , 2180–2186 (2010).
  • Spyridopoulou KP , DimouNL, HamodrakasSJ, BagosPG. Methylene tetrahydrofolate reductase gene polymorphisms and their association with methotrexate toxicity: a meta-analysis. Pharmacogenet. Genomics22(2) , 117–133 (2012).
  • Caliz R , Del Amo J, Balsa A et al. The C677T polymorphism in the MTHFR gene is associated with the toxicity of methotrexate in a Spanish rheumatoid arthritis population. Scand. J. Rheumatol.41(1) , 10–14 (2012).
  • Choe JY , LeeH, JungHY, ParkSH, BaeSC, KimSK. Methylenetetrahydrofolate reductase polymorphisms, C677T and A1298C, are associated with methotrexate-related toxicities in Korean patients with rheumatoid arthritis. Rheumatol. Int.32(6) , 1837–1842 (2012).
  • Tasbas O , BormanP, Gurhan Karabulut H, Tukun A, Yorgancioglu R. The frequency of A1298C and C677T polymorphisms of the methylentetrahydrofolate gene in Turkish patients with rheumatoid arthritis: relationship with methotrexate toxicity. Open Rheumatol. J.5 , 30–35 (2011).
  • Lee YH , SongGG. Associations between the C677T and A1298C polymorphisms of MTHFR and the efficacy and toxicity of methotrexate in rheumatoid arthritis: a meta-analysis. Clin. Drug Investig.30(2) , 101–108 (2010).
  • Mena JP , Salazar-ParamoM, Gonzalez-LopezL et al. Polymorphisms C677T and A1298C in the MTHFR gene in Mexican patients with rheumatoid arthritis treated with methotrexate: implication with elevation of transaminases. Pharmacogenomics J. 11(4) , 287–291 (2011).
  • Fisher MC , CronsteinBN. Metaanalysis of methylenetetrahydrofolate reductase (MTHFR) polymorphisms affecting methotrexate toxicity. J. Rheumatol.36(3) , 539–545 (2009).
  • Fransen J , KooloosWM, WesselsJA et al. Clinical pharmacogenetic model to predict response of MTX monotherapy in patients with established rheumatoid arthritis after DMARD failure. Pharmacogenomics 13(9) , 1087–1094 (2012).
  • Bansard C , LequerreT, DerambureC et al. Gene profiling predicts rheumatoid arthritis responsiveness to IL-1Ra (anakinra). Rheumatology (Oxford) 50(2) , 283–292 (2011).
  • Ma MH , IbrahimF, WalkerD et al. Remission in early rheumatoid arthritis: predicting treatment response. J. Rheumatol. 39(3) , 470–475 (2012).
  • Fautrel B , GrangerB, CombeB, SarauxA, GuilleminF, Le Loet X. Matrix to predict rapid radiographic progression of early rheumatoid arthritis patients from the community treated with methotrexate or leflunomide: results from the ESPOIR cohort. Arthritis Res. Ther.14(6) , R249 (2012).
  • Bulatovic M , HeijstekMW, van Dijkhuizen EH, Wulffraat NM, Pluijm SM, de Jonge R. Prediction of clinical non-response to methotrexate treatment in juvenile idiopathic arthritis. Ann. Rheum. Dis.71(9) , 1484–1489 (2012).
  • Galbiatti AL , CastroR, CaldasHC, PadovaniJA, PavarinoEC, Goloni-BertolloEM. Alterations in the expression pattern of MTHFR, DHFR, TYMS, and SLC19A1 genes after treatment of laryngeal cancer cells with high and low doses of methotrexate. Tumour Biol.34(6) , 3765–3771 (2013).
  • Stamp LK , HazlettJ, RobertsRL, FramptonC, HightonJ, HessianPA. Adenosine receptor expression in rheumatoid synovium: a basis for methotrexate action. Arthritis Res. Ther.14(3) , R138 (2012).
  • Li Y , JiangL, ZhangS et al. Methotrexate attenuates the Th17/IL-17 levels in peripheral blood mononuclear cells from healthy individuals and RA patients. Rheumatol. Int. 32(8) , 2415–2422 (2012).
  • Hobl EL , MaderRM, ErlacherL et al. The influence of methotrexate on the gene expression of the pro-inflammatory cytokine IL-12A in the therapy of rheumatoid arthritis. Clin. Exp. Rheumatol. 29(6) , 963–969 (2011).
  • Blits M , JansenG, AssarafYG et al. Methotrexate normalizes upregulated folate pathway genes in rheumatoid arthritis. Arthritis Rheum. 65(11) , 2791–2802 (2013).
  • Xie X , ZhangD, ChenJW, TianJ, LingGH, LiF. Pharmacogenomics of biological treatment in rheumatoid arthritis. Expert Opin. Biol. Ther.14(2) , 157–164 (2014).
  • Meda F , FolciM, BaccarelliA, SelmiC. The epigenetics of autoimmunity. Cell. Mol. Immunol.8(3) , 226–236 (2011).
  • Javierre BM , HernandoH, BallestarE. Environmental triggers and epigenetic deregulation in autoimmune disease. Discov. Med.12(67) , 535–545 (2011).
  • Costenbader KH , GayS, Alarcon-RiquelmeME, IaccarinoL, DoriaA. Genes, epigenetic regulation and environmental factors: which is the most relevant in developing autoimmune diseases? Autoimmun. Rev.11(8) , 604–609 (2012).
  • Renaudineau Y , YouinouP. Epigenetics and autoimmunity, with special emphasis on methylation. Keio J. Med.60(1) , 10–16 (2011).
  • Karouzakis E , GayRE, GayS, NeidhartM. Epigenetic deregulation in rheumatoid arthritis. Adv. Exp. Med. Biol.711 , 137–149 (2011).
  • Ballestar E . Epigenetic alterations in autoimmune rheumatic diseases. Nat. Rev. Rheumatol.7(5) , 263–271 (2011).
  • Owen SA , LuntM, BowesJ et al. MTHFR gene polymorphisms and outcome of methotrexate treatment in patients with rheumatoid arthritis: analysis of key polymorphisms and meta-analysis of C677T and A1298C polymorphisms. Pharmacogenomics J.13(2) , 137–147 (2013).
  • Dervieux T , WesselsJA, KremerJM et al. Patterns of interaction between genetic and nongenetic attributes and methotrexate efficacy in rheumatoid arthritis. Pharmacogenet. Genomics 22(1) , 1–9 (2012).
  • Bakker MF , CavetG, JacobsJW et al. Performance of a multi-biomarker score measuring rheumatoid arthritis disease activity in the CAMERA tight control study. Ann. Rheum. Dis. 71(10) , 1692–1697 (2012).
  • Maillefert JF , PuechalX, FalgaroneG et al. Prediction of response to disease modifying antirheumatic drugs in rheumatoid arthritis. Joint Bone Spine 77(6) , 558–563 (2010).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.