Impact of the heterozygous TPMT*1/*3C genotype on azathioprine-induced myelosuppression in kidney transplant recipients in Thailand

Clinical Therapeutics

Volumn 31, Issue 7, 2009, Pages 1524-1533

  Vannaprasaht, Suda ^a   Angsuthum, Susothorn ^a   Avihingsanon, Yingyos ^b   Sirivongs, Dhavee ^a   Pongskul, Cholatip ^a   Makarawate, Pattarapong ^a   Praditpornsilpa, Kearkiat ^b   Tassaneeyakul, Wongwiwat ^c   Tassaneeyakul, Wichittra ^a  

^a KHON KAEN UNIVERSITY   (Thailand)

^b CHULALONGKORN UNIVERSITY   (Thailand)

^c KHON KAEN UNIVERSITY   (Thailand)

Author keywords

azathioprine; kidney transplantation; myelosuppression; Thailand; TPMT genetic polymorphism; TPMT*3C

Indexed keywords

AZATHIOPRINE; CYCLOSPORIN; PREDNISOLONE; PREDNISONE; TACROLIMUS; THIOPURINE METHYLTRANSFERASE;

ADOLESCENT; ADULT; AGED; ARTICLE; BONE MARROW SUPPRESSION; BONE MARROW TOXICITY; CADAVER DONOR; CONTROLLED STUDY; DRUG STRUCTURE; DRUG WITHDRAWAL; FEMALE; GENETIC POLYMORPHISM; GENETIC RISK; GENOTYPE; HETEROZYGOSITY; HUMAN; KIDNEY TRANSPLANTATION; LEUKOPENIA; LIVING DONOR; MAJOR CLINICAL STUDY; MALE; PREVALENCE; SENSITIVITY AND SPECIFICITY; THAILAND; THROMBOCYTOPENIA;

ADOLESCENT; ADULT; AGED; ALLELES; ASIAN CONTINENTAL ANCESTRY GROUP; AZATHIOPRINE; FEMALE; GENE FREQUENCY; GENOTYPE; HEMATOLOGIC DISEASES; HETEROZYGOTE; HUMANS; IMMUNOSUPPRESSIVE AGENTS; KIDNEY TRANSPLANTATION; MALE; METHYLTRANSFERASES; MIDDLE AGED; POLYMERASE CHAIN REACTION; POLYMORPHISM, GENETIC; RETROSPECTIVE STUDIES; THAILAND; YOUNG ADULT;

EID: 68649101215     PISSN: 01492918     EISSN: 1879114X     Source Type: Journal    
DOI: 10.1016/j.clinthera.2009.07.008     Document Type: Article

References (43)

1. Vathsala A., and the Asian Transplant Registry. Immunosuppression use in renal transplantation from Asian transplant centers: A preliminary report from the Asian Transplant Registry. Transplant Proc. 36 (2004) 1868-1870
2. Yates C.R., Krynetski E.Y., Loennechen T., et al. Molecular diagnosis of thiopurine S-methyltransferase deficiency: Genetic basis for azathioprine and mercaptopurine intolerance. Ann Intern Med. 126 (1997) 608-614
3. Krynetski E.Y., and Evans W.E. Pharmacogenetics as a molecular basis for individualized drug therapy: The thiopurine S-methyltransferase paradigm. Pharm Res. 16 (1999) 342-349
4. Cara C.J., Pena A.S., Sans M., et al. Reviewing the mechanism of action of thiopurine drugs: Towards a new paradigm in clinical practice. Med Sci Monit. 10 (2004) RA247-RA254
5. Lennard L. The clinical pharmacology of 6-mercaptopurine. Eur J Clin Pharmacol. 43 (1992) 329-339
6. Deininger M., Szumlanski C.L., Otterness D.M., et al. Purine substrates for human thiopurine methyltransferase. Biochem Pharmacol. 48 (1994) 2135-2138
7. Parks D.A., and Granger D.N. Xanthine oxidase: Biochemistry, distribution and physiology. Acta Physiol Scand Suppl. 548 (1986) 87-99
8. Weinshilboum R.M. Pharmacogenomics: Catechol O-methyltransferase to thiopurine S-methyltransferase. Cell Mol Neurobiol. 26 (2006) 539-561
9. Salavaggione O.E., Wang L., Wiepert M., et al. Thiopurine S-methyltransferase pharmacogenetics: Variant allele functional and comparative genomics. Pharmacogenet Genomics. 15 (2005) 801-815
10. Krynetski E.Y., and Evans W.E. Genetic polymorphism of thiopurine S-methyltransferase: Molecular mechanisms and clinical importance. Pharmacology 61 (2000) 136-146
11. McLeod H.L., and Siva C. The thiopurine S-methyltransferase gene locus-implications for clinical pharmacogenomics. Pharmacogenomics 3 (2002) 89-98
12. Weinshilboum R. Inheritance and drug response. N Engl J Med. 348 (2003) 529-537
13. Weinshilboum R.M., and Sladek S.L. Mercaptopurine pharmacogenetics: Monogenic inheritance of erythrocyte thiopurine methyltransferase activity. Am J Hum Genet. 32 (1980) 651-662
14. Collie-Duguid E.S., Pritchard S.C., Powrie R.H., et al. The frequency and distribution of thiopurine methyl-transferase alleles in Caucasian and Asian populations. Pharmacogenetics 9 (1999) 37-42
15. Ameyaw M.M., Collie-Duguid E.S., Powrie R.H., et al. Thiopurine methyltransferase alleles in British and Ghanaian populations. Hum Mol Genet. 8 (1999) 367-370
16. Hon Y.Y., Fessing M.Y., Pui C.H., et al. Polymorphism of the thiopurine S-methyltransferase gene in African-Americans. Hum Mol Genet. 8 (1999) 371-376
17. Kumagai K., Hiyama K., Ishioka S., et al. Allelotype frequency of the thio-purine methyltransferase (TPMT) gene in Japanese. Pharmacogenetics 11 (2001) 275-278
18. Srimartpirom S., Tassaneeyakul W., Kukongviriyapan V., and Tassaneeyakul W. Thiopurine S-methyltransferase genetic polymorphism in the Thai population. Br J Clin Pharmacol. 58 (2004) 66-70
19. Schütz E., Gummert J., Mohr F., and Oellerich M. Azathioprine-induced myelo-suppression in thiopurine methyl-transferase deficient heart transplant recipient. Lancet 341 (1993) 436
20. Evans W.E., Horner M., Chu Y.Q., et al. Altered mercaptopurine metabolism, toxic effects, and dosage requirement in a thiopurine methyl-transferase-deficient child with acute lymphocytic leukemia. J Pediatr. 119 (1991) 985-989
21. Evans W.E., Hon Y.Y., Bomgaars L., et al. Preponderance of thiopurine S-methyltransferase deficiency and heterozygosity among patients intolerant to mercaptopurine or azathioprine. J Clin Oncol. 19 (2001) 2293-2301
22. Kurzawski M., Dziewanowski K., Ciechanowski K., and Droz′dzik M. Severe azathioprine-induced myelotoxicity in a kidney transplant patient with thiopurine S-methyltransferase-deficient genotype (TPMT*3A/*3C). Transpl Int. 18 (2005) 623-625
23. Song D.K., Zhao J., and Zhang L.R. TPMT genotype and its clinical implication in renal transplant recipients with azathioprine treatment. J Clin Pharm Ther. 31 (2006) 627-635
24. Kurzawski M., Dziewanowski K., Gawronska-Szklarz B., et al. The impact of thiopurine S-methyltransferase polymorphism on azathioprine-induced myelotoxicity in renal transplant recipients. Ther Drug Monit. 27 (2005) 435-441
25. Formea C.M., Myers-Huentelman H., Wu R., et al. Thiopurine S-methyltransferase genotype predicts azathioprine-induced myelotoxicity in kidney transplant recipients. Am J Transplant 4 (2004) 1810-1817
26. Sebbag L., Boucher P., Davelu P., et al. Thiopurine S-methyltransferase gene polymorphism is predictive of azathioprine-induced myelosuppression in heart transplant recipients. Transplantation 69 (2000) 1524-1527
27. Breen D.P., Marinaki A.M., Arenas M., and Hayes P.C. Pharmacogenetic association with adverse drug reactions to azathioprine immunosuppressive therapy following liver transplantation [published correction appears in Liver Transpl. 2005;11:1150]. Liver Transpl. 11 (2005) 826-833
28. Pandya B., Thomson W., Poulton K., et al. Azathioprine toxicity and thio-purine methyltransferase genotype in renal transplant patients. Transplant Proc. 34 (2002) 1642-1645
29. Tassaneeyakul W., Srimarthpirom S., Reungjui S., et al. Azathioprine-induced fatal myelosuppression in a renal-transplant recipient who carried heterozygous TPMT*1/*3C. Transplantation 76 (2003) 265-266
30. Hongeng S., Sasanakul W., Chuansumrit A., et al. Frequency of thiopurine S-methyltransferase genetic variation in Thai children with acute leukemia. Med Pediatr Oncol. 35 (2000) 410-414
31. Ford L.T., and Berg J.D. Determination of thiopurine S-methyltransferase activity in erythrocytes using 6-thioguanine as substrate and a non-extraction liquid chromatographic technique. J Chromatogr B Analyt Technol Biomed Life Sci. 798 (2003) 111-115
32. In: Bland M. (Ed). An Introduction to Medical Statistics. 2nd ed. (1995), Oxford University Press, New York, NY
33. Gisbert J.P., and Gomollón F. Thiopurine-induced myelotoxicity in patients with inflammatory bowel disease: A review. Am J Gastroenterol. 103 (2008) 1783-1800
34. Boulieu R., Lenoir A., Bertocchi M., and Mornex J.F. Intracellular thiopurine nucleotides and azathioprine myelo-toxicity in organ transplant patients. Br J Clin Pharmacol. 43 (1997) 116-118
35. Duley J.A., and Florin T.H. Thiopurine therapies: Problems, complexities, and progress with monitoring thioguanine nucleotides. Ther Drug Monit. 27 (2005) 647-654
36. Murphy L.A., and Atherton D. A retrospective evaluation of azathioprine in severe childhood atopic eczema, using thiopurine methyltransferase levels to exclude patients at high risk of myelosuppression. Br J Dermatol. 147 (2002) 308-315
37. Regueiro M., and Mardini H. Determination of thiopurine methyltransferase genotype or phenotype optimizes initial dosing of azathioprine for the treatment of Crohn's disease. J Clin Gastroenterol. 35 (2002) 240-244
38. Kaskas B.A., Louis E., Hindorf U., et al. Safe treatment of thiopurine S-methyltransferase deficient Crohn's disease patients with azathioprine. Gut. 52 (2003) 140-142
39. Gearry R.B., Barclay M.L., Roberts R.L., et al. Thiopurine methyltransferase and 6-thioguanine nucleotide measurement: Early experience of use in clinical practice. Intern Med J. 35 (2005) 580-585
40. Weyer N., Kröplin T., Fricke L., and Iven H. Human thiopurine S-methyltransferase activity in uremia and after renal transplantation. Eur J Clin Pharmacol. 57 (2001) 129-136
41. Yan L., Zhang S., Eiff B., et al. Thiopurine methyltransferase polymorphic tandem repeat: Genotype-phenotype correlation analysis. Clin Pharmacol Ther. 68 (2000) 210-219
42. Marinaki A.M., Ansari A., Duley J.A., et al. Adverse drug reactions to azathioprine therapy are associated with polymorphism in the gene encoding inosine triphosphate pyrophosphatase (ITPase). Pharmacogenetics 14 (2004) 181-187
43. Stocco G., Martelossi S., Barabino A., et al. Glutathione-S-transferase genotypes and the adverse effects of azathioprine in young patients with inflammatory bowel disease. Inflamm Bowel Dis. 13 (2007) 57-64