• 1
    Weinshilboum RM, Raymond FA, Pazmino PA. Human erythrocyte thiopurine methyltransferase: radiochemical microassay and biochemical properties. Clin Chim Acta 1978; 85: 323333.
  • 2
    Weinshilboum RM, Sladek SL. Mercaptopurine pharmacogenetics: monogenic inheritance of erythrocyte thiopurine methyltransferase activity. Am J Hum Genet 1980; 32: 651662.
  • 3
    Van Loon J, Weinshilboum RM. Thiopurine methyltransferase biochemical genetics: human lymphocyte activity. Biochem Genet 1982; 20: 637658.
  • 4
    Woodson LC, Dunnette JH, Weinshilboum RM. Pharmacogenetics of human thiopurine methyltransferase: kidney-erythrocyte correlation and immunotitration studies. J Pharmacol Exp Ther 1982; 222: 174181.
  • 5
    Szumlanski CL, Honchel R, Scott MC, Weinshilboum RM. Human liver thiopurine methyltransferase pharmacogenetics: biochemical properties, liver-erythrocyte correlation and presence of isozymes. Pharmacogenetics 1992; 2: 148159.
  • 6
    Krynetski EY, Schuetz JD, Galpin AJ, Pui C-H, Relling MV, Evans WE. A single point mutation leading to loss of catalytic activity in human thiopurine S-methyltransferase. Proc Natl Acad Sci U S A 1995; 92: 949953.
  • 7
    Szumlanski C, Otterness D, Her C, Lee D, Brandriff B, Kelsell D, Spurr N, Lennard L, Weiben E, Weinshilboum R. Thiopurine methyltransferase pharmacogenetics: human gene cloning and characterization of a common genetic polymorphism. DNA Cell Biol 1996; 15: 1730.
  • 8
    Otterness D, Szumlanski C, Lennard L, Klemetsdal B, Aarbakke J, Park-Hah JO, Iven H, Schmeigelow K, Branum E, O'Brien J, Weinshilboum RM. Human thiopurine methyltransferase pharmacogenetics: gene sequence polymorphisms. Clin Pharmacol Ther 1997; 62: 6073.
  • 9
    Wang L, Weinshilboum R. Thiopurine S-methyltransferase pharmacogenetics: insights, challenges and future directions. Oncogene 2006; 25: 16291638.
  • 10
    Lennard L, Van Loon JA, Weinshilboum RM. Pharmacogenetics of acute azathioprine toxicity: relationship to thiopurine methyltransferase genetic polymorphism. Clin Pharmacol Ther 1989; 46: 149154.
  • 11
    Flockhart DA, Skaar T, Klein TE, Nguyen AT. Clinically available pharmacogenomics tests. Clin Pharmacol Ther 2009; 86: 109113.
  • 12
    Holme SA, Duley JA, Sanderson J, Routledge PA, Anstey AV. Erythrocyte thiopurine methyltransferase assessment prior to azathioprine use in the UK. Q J Med 2002; 95: 439444.
  • 13
    Ford LT, Berg JD. ThiopurineS-methyltransferase (TPMT) assessment prior to starting thiopurine drug treatment; a pharmacogenomic test whose time has come. J Clin Pathol 2010; 63: 288295.
  • 14
    Relling MV, Gardner EE, Sandborn WJ, Pui C-H, Stein CM, Carrillo M, Evans WE, Klein TE. Clinical pharmacogenetics implementation consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing. Clin Pharmacol Ther 2011; 89: 387391.
  • 15
    Relling MV, Gardner EE, Sandborn WJ, Schmiegelow K, Pui C-H, Yee SW, Stein CM, Carrillo M, Evans WE, Hicks JK, Schwab M, Klein TE. Clinical pharmacogenetics implementation consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing: 2013 update. Clin Pharmacol Ther 2013; 93: 324325.
  • 16
    Lennard L, Murphy MF, Maddocks JL. Severe megaloblastic anaemia associated with abnormal azathioprine metabolism. Br J Clin Pharmacol 1984; 17: 171172.
  • 17
    Maddocks JL, Lennard L, Amess J, Amos R, Meyrick-Thomas R. Azathioprine and severe bone marrow depression. Lancet 1986; 327: 156.
  • 18
    Evans WE, Horner M, Chu YQ, Kalwinsky D, Roberts WM. Altered mercaptopurine metabolism, toxic effects, and dosage requirement in a thiopurine methyltransferase deficient child with acute lymphoblastic leukaemia. J Pediatr 1991; 119: 985989.
  • 19
    Schutz E, Gummert J, Mohr F, Oellerich M. Azathioprine-induced myelosuppression in thiopurine methyltransferase deficient heart transplant recipient. Lancet 1993; 341: 436.
  • 20
    McBride KL, Gilchrist GS, Smithson WA, Weinshilboum RM, Szumlanski CL. Severe 6-thioguanine-induced marrow aplasia in a child with acute lymphoblastic leukaemia and inherited thiopurine methyltransferase deficiency. J Ped Hematol Oncol 2000; 22: 441445.
  • 21
    Konstantopoulou M, Belgi A, Griffiths KD, Macfarlane AW. Azathioprine-induced pancytopenia in a patient with pompholyx and deficiency of erythrocyte thiopurine methyltransferase. Br Med J 2005; 330: 350351.
  • 22
    Tidd DM, Paterson ARP. A biochemical mechanism for the delayed cytotoxic reactions of 6-mercaptopurine. Cancer Res 1974; 34: 738746.
  • 23
    Karran P. Thiopurines, DNA damage, DNA repair and therapy-related cancer. Br Med Bull 2006; 79 and 80: 153170.
  • 24
    Tiede I, Fritz G, Strand S, Poppe D, Dvorsky R, Strand D, Lehr HA, Wirtz S, Becker C, Atreya R, Mudter J, Hildner K, Bartsch B, Holtman M, Blumberg R, Walczak H, Iven H, Galle PR, Ahmadian MR, Neurath MF. CD28-dependent Rac1 activation is the molecular target of azathioprine in primary human CD4+ T lymphocytes. J Clin Invest 2003; 111: 11331145.
  • 25
    Poppe D, Tielde I, Fritz G, Becker C, Bartsch B, Wirtz S, Strand D, Tanaka S, Galle PR, Bustelo XR, Neurath MF. Azathioprine suppresses Ezrin-Radixin-Moesin-dependent T cell-APC conjugation through inhibition of Vav guanosine exchange activity on Rac proteins. J Immunol 2006; 176: 640651.
  • 26
    Bourgine J, Garat A, Allorge D, Crunelle-Thibaut A, Lo-Guidice JM, Colombel JF, Brolly F, Billaut-Laden I. Evidence for a functional genetic polymorphism of Rho-GTPase Rac1. Implication in azathioprine response? Pharmacogenet Genomics 2011; 21: 313324.
  • 27
    Lennard L, Lilleyman JS, Van Loon JA. Weinshilboum RM Genetic variation in response to 6-mercaptopurine for childhood acute lymphoblastic leukaemia. Lancet 1990; 336: 225229.
  • 28
    Relling MV, Hancock ML, Rivera GK, Sandlund JT, Ribeiro RC, Krynetski EY, Pui C-H EWE. Mercaptopurine therapy intolerance and heterozygosity at the thiopurine S-methyltransferase gene locus. J Natl Cancer Inst 1999; 91: 20012008.
  • 29
    Lennard L, Lilleyman JS. Variable 6-mercaptopurine metabolism and treatment outcome in childhood lymphoblastic leukaemia [published erratum appears in J Clin Oncol 1990; 8: 567]. J Clin Oncol 1989; 7: 18161823.
  • 30
    Schmiegelow K, Schroder H, Gustafsson G, Kristinsson J, Glomstein A, Salmi T, Wranne L. Risk of relapse in childhood acute lymphoblastic leukaemia is related to RBC methotrexate and mercaptopurine metabolites during maintenance chemotherapy. J Clin Oncol 1995; 13: 345351.
  • 31
    Balis FM Holcenberg JS, Poplack DG, Ge J, Sather HN, Murphy RF, Ames MM, Waskerwitz MJ, Tubergen DG, Zimm S, Gilchrist GS, Bleyer WA. Pharmacokinetics and pharmacodynamics of oral methotrexate and mercaptopurine in children with lower risk acute lymphoblastic leukaemia: a joint Children's Cancer Group and Pediatric Oncology Branch study. Blood 1998; 92: 35693577.
  • 32
    Schmiegelow K, Bjork O, Glomstein A, Gustafsson G, Keilding N, Kristinsson J, Makipernaa A, Rosthoj S, Szulmlanski C, Sorensen TM, Weinshilboum R. Intensification of mercaptopurine/methotrexate maintenance chemotherapy may increase the risk of relapse for some children with acute lymphoblastic leukaemia. J Clin Oncol 2003; 21: 13321339.
  • 33
    Relling MV, Pui C-H, Cheng C, Evans WE. Thiopurine methyltransferase in acute lymphoblastic leukaemia. Blood 2006; 107: 843844.
  • 34
    Nelson JA. Mechanisms of action of thiopurines used in the curative therapy for childhood leukaemias. Cancer Bull 1992; 44: 470473.
  • 35
    Dervieux T, Brenner TL, Hon YY, Zhou Y, Hancock ML, Sandlund JT, Rivera GK, Ribeiro PC, Boycott JM, Pui C-H, Relling MV, Evans WE. De novo purine synthesis inhibition and antileukaemic effects of mercaptopurine alone or in combination with methotrexate in vivo. Blood 2002; 100: 12401247.
  • 36
    Lennard L, Cartwright CS, Wade R, Richards SM, Vora A. Thiopurine methyltransferase genotype-phenotype discordance, and thiopurine active metabolite formation, in childhood acute lymphoblastic leukaemia. Br J Clin Pharmacol 2013; 76: 125136.
  • 37
    Cuffari C, Theoret Y, Latour S, Seidman G. 6-Mercaptopurine metabolism in Crohn's disease: correlation with efficacy and toxicity. Gut 1996; 39: 401406.
  • 38
    Lowry P, Franklin CL, Weaver AL, Gennett Pike M, Mays DC, Tremaine WJ, Lipsky JJ, Sandborn WJ. Measurement of thiopurine methyltransferase activity and azathioprine metabolites in patients with inflammatory bowel disease. Gut 2001; 49: 665670.
  • 39
    Dubinsky MC, Lamothe S, Yang HY, Targan SR, Sinnett D, Theoret Y, Seidman EG. Pharmacogenetics and metabolite measurement for 6-mercaptopurine therapy in inflammatory bowel disease. Gastroenterology 2000; 118: 705713.
  • 40
    Dubinsky MC, Yang HY, Hassard PV, Seidman EG, Kam LY, Abreu MT, Targan SR, Vasiliauskas EA. 6-MP metabolite profiles provide a biochemical explanation for 6-MP resistance in patients with inflammatory bowel disease. Gastroenterology 2002; 122: 904915.
  • 41
    Wright S, Sanders DS, Lobo A, Lennard L. Clinical significance of azathioprine active metabolite concentrations on inflammatory bowel disease. Gut 2004; 53: 11231128.
  • 42
    Campbell S, Kingstone K, Ghosh S. Relevance of thiopurine methyltransferase activity in inflammatory bowel disease patients maintained on low dose azathioprine. Aliment Pharmacol Ther 2002; 16: 389398.
  • 43
    Hindorf U, Lindqvist M, Hildebrand H, Fagerberg U, Almers S. Adverse events leading to modification of therapy in a large cohort of patients with inflammatory bowel disease. Aliment Pharmacol Ther 2006; 24: 331342.
  • 44
    Gisbert JP, Nino P, Rodrigo L, Cara C, Guijarro LG. Thiopurine methyltransferase (TPMT) activity and adverse effects of azathioprine in inflammatory bowel disease: long-term follow-up study of 394 patients. Am J Gastroenterol 2006; 101: 27692776.
    Direct Link:
  • 45
    Dubinsky MC, Reyes E, Ofman J, Chiou C-F, Wade S, Sandborn WJ. A cost-effectiveness analysis of alternative disease management strategies in patients with Crohn's disease treated with azathioprine or 6-mercaptopurine. Am J Gastroenterol 2005; 100: 22392247.
    Direct Link:
  • 46
    Woodson LC, Ames MM, Selassie CD, Hansch C, Weinshilboum RM. Thiopurine methyltransferase. Aromatic thiol substrates and inhibition by benzoic acid derivatives. Mol Pharmacol 1983; 24: 471478.
  • 47
    Glauser TA, Nelson MD, Zembower DE, Lipsky JJ, Weinshilboum RM. Diethylthiocarbamate S-methylation: evidence for catalysis by human liver thiol methyltransferase and thiopurine methyltransferase. J Pharm Expt Therap 1993; 266: 2332.
  • 48
    Deininger M, Szumlanski CL, Otterness DM, Van Loon J, Ferber W, Weinshilboum RM. Purine substrates for human thiopurine methyltransferase. Biochem Pharmacol 1994; 11: 21352138.
  • 49
    Rowland K, Lennard L, Lilleyman JS. High performance liquid chromatographic assay of methylthioguanine nucleotides. J Chromatogr B 1998; 705: 2937.
  • 50
    Szumlanski C, Weinshilboum RM. Sulfsalazine inhibition of thiopurine methyltransferase: possible mechanism for interaction with 6-mercaptopurine. Br J Clin Pharmacol 1995; 39: 456459.
  • 51
    Lewis LD, Benin A, Szumlanski CL, Otterness DM, Lennard L, Weinshilboum RM, Nierenberg DW. Olsalazine and 6-mercaptopurine-related bone marrow suppression: a possible drug-drug interaction. Clin Pharmacol Ther 1997; 62: 464475.
  • 52
    Hande S, Wilson-Rich N, Bousvaros A, Zholudev A, Maurer R, Banks P, Makrauer F, Reddy S, Burakoff R, Friedman S. 5-Aminosalicylate therapy is associated with higher 6-thioguanine levels in adults and children with inflammatory bowel disease in remission on 6-mercaptopurine or azathioprine. Inflamm Bowel Dis 2006; 12: 251257.
  • 53
    de Boer NKH, Wong DR, Jharap B, de Graaf P, Hooymans PM, Mulder CJJ, Rijmen F, Engels LGJB, van Bodegraven AA. Dose-dependent influence of 5-aminosalicylates on thiopurine metabolism. Am J Gastroenterol 2007; 102: 27472753.
    Direct Link:
  • 54
    Shipkova M, Niedmann PD, Armstrong VM, Oellerich M, Wieland E. Determination of thiopurine methyltransferase activity in isolated human erythrocytes does not reflect putative in vivo enzyme inhibition by sulfasalazine. Clin Chem 2004; 50: 438441.
  • 55
    Thiopurine methyltransferase (TPMT) test. Rochester Test Catalog. Mayo Clinic, Medical Laboratories, Rochester, MN 55095, USA. Available at (last accessed 17 September 2013).
  • 56
    TPMT testing. Prometheus Laboratories Inc, Therapeutics and Diagnostics, 9410 Carroll Park Drive, San Diego, CA 92121-4203. Available at (last accessed 17 September 2013).
  • 57
    Dervieux T, Meyer G, Barham R, Matsutani M, Barry M, Boulieu R, Neri B, Seidman E. Liquid chromatography-tandem mass spectrometry analysis of erythrocyte thiopurine nucleotides and effects of thiopurine methyltransferase gene variants on these metabolites in patients receiving azathioprine/6-mercaptopurine therapy. Clin Chem 2005; 51: 20742084.
  • 58
    TPMT Test. GSTS Pathology, Biochemical Sciences, Purine laboratory, 4th Floor North Wing, St Thomas' Hospital, London SE1 7EH. Available at (last accessed 17 September 2013).
  • 59
    Thiopurine S-methyltransferase (TPMT) City assays, Biochemistry Tests, Department of Clinical Biochemistry, City Hospital, Dudley Road, Birmingham, B18 7QH. Available at (last accessed 17 September 2013).
  • 60
    TPMT gene. Royal College of Pathologists of Australia. Catalogue of genetic tests and laboratories. Available at (last accessed 17 September 2013).
  • 61
    Lennard L, Singleton HJ. High performance liquid chromatographic assay of human red blood cell thiopurine methyltransferase activity. J Chromatogr B 1994; 661: 2533.
  • 62
    Lennard L, Richards S, Cartwright CS, Mitchell C, Lilleyman JS, Vora AJ. The thiopurine methyltransferase genetic polymorphism is associated with thioguanine-related veno-occlusive disease of the liver in children with acute lymphoblastic leukaemia. Clin Pharmacol Ther 2006; 80: 375383.
  • 63
    Kröplin T, Fisher C, Iven H. Inhibition of thiopurine S-methyltransferase activity by impurities in commercially available substrates: a factor for differing results for TPMT measurements. Eur J Clin Pharmacol 1999; 55: 285291.
  • 64
    Schaeffeler E, Fisher C, Brockmeier D, Wernet D, Moerike K, Eichelbaum M, Zanger UM, Schwab M. Comprehensive analysis of thiopurine S-methyltransferase phenotype-genotype correlation in a large population of German-caucasians and identification of novel TPMT variants. Pharmacogenetics 2004; 14: 407417.
  • 65
    Lennard L, Chew TS, Lilleyman JS. Human thiopurine methyltransferase activity varies with red blood cell age. Br J Clin Pharmacol 2001; 52: 539546.
  • 66
    Lindqvist M, Hindorf U, Almer S, Soderkvist P, Strom M, Hjortswang H, Peterson C. No induction of thiopurine methyltransferase during thiopurine treatment in inflammatory bowel disease. Nucleosides Nucleotides Nucleic Acids 2006; 25: 10331037.
  • 67
    Dilger K, Schaeffeler E, Lukas M, Strauch U, Herfarth H, Muller R, Schwab M. Monitoring of thiopurine methyltransferase activity in postsurgical patients with Crohn's disease during 1 year of treatment with azathioprine. Ther Drug Monit 2007; 29: 15.
  • 68
    Oselin K, Anier K, Tamm R, Kallassalu K, Mäeorg M. Determination of thiopurine S-methyltransferase (TPMT) activity by comparing various normalisation factors: reference values for Estonian population using HPLC-UV assay. J Chromatog B 2006; 834: 7783.
  • 69
    Brouwer C, De Abreu RA, Keizer-Garritsen JJ, Lambooy LHJ, Ament K, ter Riet PGJH, van Wering ER, Trijbels FJM, Veerman AJP, Hooherbrugge PM, Bokkerink JPM. Thiopurine methyltransferase in acute lymphoblastic leukaemia: biochemical and molecular biological aspects. Eur J Cancer 2005; 41: 613623.
  • 70
    McLeod HL, Relling MV, Liu Q, Pui C-H, Evans WE. Polymorphic thiopurine methyltransferase in erythrocytes is indicative of activity in leukemic blasts from children with acute lymphoblastic leukemia. Blood 1995; 7: 18971902.
  • 71
    Gisbert JP, Gomollon F, Cara C, Luna M, Gonzalez-Lama Y, Pajares JM, Mate J, Guijarro LG. Thiopurine methyltransferase activity in Spain: a study of 14,545 patients. Dig Dis Sci 2007; 52: 12621269.
  • 72
    Serpe L, Calvo PL, Muntoni E, D'Antico S, Giaccone M, Avagnina A, Baldi M, Barbera B, Curti F, Pera A, Eandi M, Zara GP, Canaparo R. Thiopurine S-methyltransferase pharmacogenetics in a large-scale healthy Italian-Caucasian population: differences in enzyme activity. Pharmacogenomics 2009; 10: 17531765.
  • 73
    McLeod HL, Krynetski EY, Williams JA, Evans WE. Higher activity of polymorphic thiopurine S-methyltransferase in erythrocytes from neonates compared to adults. Pharmacogenetics 1995; 5: 281286.
  • 74
    de Boer NKH, van Bodegraven AA, de Graaf P, van der Hulst RWM, Zoetekouw L, van Kuilenburg ABP. Paradoxical elevated thiopurine S-methyltransferase activity after pancytopenia during azathioprine therapy: potential influence of red blood cell age. Ther Drug Monit 2008; 30: 390393.
  • 75
    Klemetsdal B, Wiat E, Aarbakke J. Gender difference in red blood cell thiopurine methyltransferase activity. Scand J Clin Lab Invest 1993; 53: 747749.
  • 76
    Karas-Kuzelicki N, Milek M, Mlinaric-Rascan I. MTHFR and TYMS genotypes influence TPMT activity and its differential modulation in males and females. Clin Biochem 2010; 43: 3742.
  • 77
    McLeod HL, Lin J-S, Scott EP, Pui C-H, Evans WE. Thiopurine methyltransferase activity in American White subjects and Black subjects. Clin Pharmacol Ther 1994; 55: 1520.
  • 78
    Klemetsdal B, Tollefsen E, Loennechen T, Johnsen K, Utsi E, Gisholt K, Wist E, Aarbaake J. Interethnic differences in thiopurine methyltransferase activity. Clin Pharmacol Ther 1992; 51: 2431.
  • 79
    Klemetsdal B, Straume B, Wist E, Aarbakke J. Identification of factors regulating thiopurine methyltransferase activity in a Norwegian population. Eur J Clin Pharmacol 1993; 44: 147152.
  • 80
    Kham SKY, Soh CK, Liu TC, Chan YH, Ariffin H, Tan PL, Yeoh AEJ. Thiopurine S-methyltransferase activity in three major Asian populations: a population-based study in Singapore. Eur J Clin Pharmacol 2008; 64: 373379.
  • 81
    Kham SKY, Tan PL, Tay AHN, Heng CK, Yeoh AEJ, Quah T-C. Thiopurine methyltransferase polymorphisms in a multiracial Asian population and children with acute lymphoblastic leukaemia. J Pediatr Haematol Oncol 2002; 24: 353359.
  • 82
    Park-Hah JO, Klementsdal B, Lyssa R, Choi KH, Aarbakke J. Thiopurine emthyltransferase activity in a Korean population sample of children. Clin Pharmacol Ther 1996; 60: 6874.
  • 83
    Collie-Duguid ESR, Pritchard SC, Powrie RH, Sludden J, Collier DA, McLeod HL. The frequency and distribution of thiopurine methyltransferase alleles in Caucasian and Asian populations. Pharmacogenetics 1999; 9: 3742.
  • 84
    McLeod HL, Pritchard SC, Githhang J, Indalo A, Ameyaw M-M, Powrie RH, Booth L, Collie-Duguid ESR. Ethnic differences in thiopurine methyltransferase pharmacogenetics: evidence for allele specificity in Caucasian and Kenyan individuals. Pharmacogenetics 1999; 9: 773776.
  • 85
    McLeod HL, Siva C. The thiopurine S-methyltransferase gene locus – implications for clinical pharmacogenomics. Pharmacogenetics 2002; 3: 8998.
  • 86
    Hon YY, Fessing MY, Pui C-H, Relling MV, Krynerski EY, Evans WE. Polymorphisms of the thiopurine S-methyltransferase gene in African-Americans. Hum Mol Genet 1999; 8: 371376.
  • 87
    Appell ML, Berg J, Duley J, Evans WE, Kennedy MA, Lennard L, Marinaki T, McLeod HL, Relling MV, Schaeffeler E, Schwab M, Weinshilboum R, Yeoh AEJ, McDonagh EM, Hebert JM, Klein TE, Coulthard SA. Nomenclature for alleles of the thiopurine methyltransferase (TPMT) gene. Pharmacogenet Genomics 2013; 23: 242248.
  • 88
    TPMT Nomenclature Committee. TPMT alleles. Available at (last accessed 17 September 2013).
  • 89
    Booth RA, Ansari MT, Loit E, Tricco AC, Weeks L, Doucette S, Skidmore B, Sears M, Sy R, Karsh J. Assessment of thiopurine S-methyltransferase activity in patients prescribed thiopurines: a systematic review. Ann Intern Med 2011; 154: 814823.
  • 90
    Spire-Vayron de la Moureyre C, Debuysere H, Fazio F, Sergent E, Bernard C, Sabbagh N, Marez D, Lo Guidice JM, D'halluim J-C, Broly F. Characterization of a variable number tandem repeat region in the thiopurine S-methyltransferase gene promoter. Pharmacogenetics 1999; 9: 189198.
  • 91
    Yan L, Zhang S, Eiff B, Szumlanski CL, Powers M, O'Brien JF, Weinshilboum RM. Thiopurine methyltransferase polymorphic tandem repeat: genotype-phenotype correlation analysis. Clin Pharmacol Ther 2000; 68: 210219.
  • 92
    Ford L, Kampanis P, Berg J. Thiopurine S-methyltransferase genotype-phenotype concordance: used as a quality assurance tool to help control the phenotype assay. Ann Clin Biochem 2009; 46: 152154.
  • 93
    Hindorf U, Appell ML. Genotyping should be considered the primary choice for pre-treatment evaluation of thiopurine methyltransferase function. J Crohn's Colitis 2012; 6: 655659.
  • 94
    Fakoury M, Andreu-Gallien J, Mahr A, Medard Y, Azougagh S, Vilmer E, Jacqz-Aigrain E. Should TPMT genotype and activity be used to monitor 6-mercaptopurine treatment in children with acute lymphoblastic leukaemia? J Clin Pharm Ther 2007; 32: 633639.
  • 95
    van Egmond R, Chin P, Zhang M, Sies CW, Barclay ML. High TPMT enyzyme activity does not explain drug resistance due to preferential 6-methylmercaptopurine production in patients on thiopurine treatment. Aliment Pharmacol Ther 2012; 35: 11811189.
  • 96
    Gardiner S, Gearry RB, Barclay ML, Begg EJ. Two cases of thiopurine methyltransferase (TPMT) deficiency – a lucky save and a near miss with azathioprine. Br J Clin Pharmacol 2005; 62: 473476.
  • 97
    Marra CA, Esdaile JM, Anis AH. Practical pharmacogenetics: the cost effectiveness of screening for thiopurine s-methyltransferase polymorphisms in patients with rheumatological conditions treated with azathioprine. J Rheumatol 2002; 29: 25072512.
  • 98
    Gauba V, Saldanha M, Vize C, Saleh GM. Thiopurine methyltransferase screening before azathioprine therapy. Br J Opthalmol 2006; 90: 923924.
  • 99
    Fargher EA, Tricker K, Newman W, Elliott R, Roberts SA, Shaffer JL, Bruce I, Payne K. Current use of pharmacogenetic testing: a national surveyof thiopurine methyltransferase testing prior to azathioprine prescription. J Clin Pharm Ther 2007; 32: 187195.
  • 100
    Roblin X, Oussalah A, Chevaux J-B, Sparrow M, Peyrin-Biroulet L. Use of thiopurine testing in the management of inflammatory bowel diseases in clinical practice: a worldwide survey of experts. Inflamm Bowel Dis 2011; 17: 24802487.
  • 101
    UK ALL2011 trial protocol, version 1.0, August 2011. United Kingdom trial for children and young adults with acute lymphoblastic leukaemia and lymphoma. International standard randomised controlled trial number (ISRCTN) 64515327, Section 7.12.2 and Appendix 21.
  • 102
    Higgs JE, Payne K, Roberts C, Newman WG. Are patients with intermediate TPMT activity at increased risk of myelosuppression when taking thiopurine mediactions? Pharmacogenomics 2010; 11: 177188.
  • 103
    Meggitt SJ, Gray JC, Reynolds NJ. Azathioprine dosed by thiopurine methyltransferase activity for moderate-to-severe atopic eczema; a double-blind, randomised controlled trial. Lancet 2006; 367: 839846.
  • 104
    British National Formulary online. Mercaptopurine, section 8.2.1. Available at (last accessed 17 September 2013).
  • 105
    Anstey AV, Wakelin S, Reynolds NJ. Guidelines for prescribing azathioprine in dermatology. Br J Dermatol 2004; 151: 11231132.
  • 106
    Meggitt SJ, Anstey AV, Mustapa MF, Reynolds NJ, Wakelin S. British Association of Dermatologists' guidelines for the safe and effective prescribing of azathioprine 2011. Br J Dermatol 2011; 165: 711734.
  • 107
    Chakravarty K, McDonald H, Pullar T, Taggart A, Chalmers R, Oliver S, Mooney J, Somerville M, Bosworth A, Kennedy T. BSR/BHPR guideline for disease-modifying anti-rheumatic drug (DMARD) therapy in consultation with the British Association of Dermatologists. Rheumatology 2008; 47: 924925.
  • 108
    Gleeson D, Heneghan MA. British Society of Gastroenterology (BSG) guidelines for management of autoimmune hepatitis. Gut 2012; 60: 16111629.
  • 109
    Manns MP, Czaja AJ, Gorham JD, Krawitt EL, Mieli-Vergani G, Vergani D, Vierling JM. AASLD Practice Guidelines. Diagnosis and management of autoimmune hepatitis. Hepatology 2010; 51: 21932213.
  • 110
    Carter MJ, Lobo AJ, Travis SPL. Guidelines for the management of inflammatory bowel disease in adults. Gut 2004; 53: (Suppl. 5): v116.
  • 111
    Mowat C, Cole A, Windsor A, Ahmad T, Arnott I, Driscoll R, Mitton S, Orchard T, Rutter M, Younge L, Lees C, Ho G, Satsangi J, Bloom S. Guidelines for the management of inflammatory bowel disease in adults. Gut 2011; 60: 571607.
  • 112
    Anon. TPMT testing before azathioprine therapy? Drug Ther Bull 2009; 47: 912.
  • 113
    Payne K, Newman W, Fargher E, Tricker K, Bruce IN, Ollier WER. TPMT testing in rheumatology: any better than routine monitoring? Rheumatology 2007; 46: 727729.
  • 114
    Newman WG, Payne K, Tricker K, Roberts SA, Fargher E, Pushpakom S, Alder JE, Sidgwick GP, Payne D, Elliott RA, Heise M, Elles R, Ramsden SC, Andrews J, Houston JB, Qasim F, Shaffer J, Griffiths CEM, Ray DW, Bruce I, Ollier WER. A pragmatic randomised controlled trial of thiopurine methyltransferase genotyping prior to azathioprine treatment: the TARGET study. Pharmacogenomics 2011; 12: 815826.