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dc.contributor.authorFerreira, Guilherme Motta Antunes-
dc.date.available2022-08-05-
dc.date.available2022-08-11T16:43:04Z-
dc.date.issued2020-08-27-
dc.identifier.urihttp://repositorioinstitucional.uea.edu.br//handle/riuea/4109-
dc.description.abstractReduced function alleles in the TPMT and NUDT15 genes are risk factors for thiopurine toxicity. This study evaluated the influence of Native ancestry on the distribution of TPMT (rs1142345, rs1800460 and rs1800462) and NUDT15 (rs116855232) polymorphisms and compound metabolic phenotypes in 128 healthy males from the Brazilian Amazon. The average proportion of Native and European ancestry differed greatly and significantly between self-declared Amerindians and non-Amerindians, although extensive admixture in both groups was evident. Native ancestry was not significantly associated with the frequency distribution of the TPMT or NUDT15 polymorphisms investigated. This study reported a nominal but not significant difference in the lower allele frequency between the NAT (7.7%) and non-NAT (4.2%) sub-cohorts and this quantitative discrepancy cannot be explained by the extensive native ancestry, since that analyzed sub-cohorts with ancestry> 70% vs. <30% native. Greater care should be taken with the Native American population in order not to extrapolate the pharmacogenetic data, as it is never known whether the person may be a carrier of a bad or intermediate metabolizing phenotype for TPMT or NUDT15, thus avoiding possible intoxicationpt_BR
dc.languageporpt_BR
dc.publisherUniversidade do Estado do Amazonaspt_BR
dc.rightsAcesso Abertopt_BR
dc.subjectFarmacogenéticpt_BR
dc.subjectLeucemia Linfoblástica Agudapt_BR
dc.subjectTPMTpt_BR
dc.subjectNUDT15pt_BR
dc.subjectOstra białaczka limfoblastycznapt_BR
dc.titlePrevalência dos polimorfismos da proteína NUDS15 e TPMT na Amazônia Brasileirapt_BR
dc.title.alternativePrevalence of NUDS15 and TPMT protein polymorphisms in the Brazilian Amazonpt_BR
dc.typeDissertaçãopt_BR
dc.date.accessioned2022-08-11T16:43:04Z-
dc.contributor.advisor-co1Ferreira , Cristina Motta-
dc.contributor.advisor-co1Latteshttp://lattes.cnpq.br/7283507436511006pt_BR
dc.contributor.advisor1Lacerda, Marcus Vinícius Guimarães de-
dc.contributor.advisor1Latteshttp://lattes.cnpq.br/8492376468047417pt_BR
dc.contributor.referee1Melo, Gisely Cardoso de-
dc.contributor.referee1Latteshttp://lattes.cnpq.br/5566457348830121pt_BR
dc.contributor.referee2Passos, Leny Nascimento da Motta-
dc.contributor.referee2Latteshttp://lattes.cnpq.br/8194622149198642pt_BR
dc.contributor.referee3Sampaio , Vanderson de Souza-
dc.contributor.referee3Latteshttp://lattes.cnpq.br/0039836167659650pt_BR
dc.description.resumoAlelos de função reduzida nos genes TPMT e NUDT15 são fatores de risco para a toxicidade da tiopurina. Este estudo avaliou a influência da ancestralidade nativa na distribuição de polimorfismos TPMT (rs1142345, rs1800460 e rs1800462) e NUDT15 (rs116855232) e fenótipos metabólicos compostos em 128 homens saudáveis da Amazônia brasileira. A proporção média de ancestrais nativos e europeus diferia muito e significativamente entre os autodeclarados ameríndios e não-ameríndios, embora fosse evidente uma grande mistura em ambos os grupos. A ascendência nativa não foi significativamente associada à distribuição de frequência dos polimorfismos TPMT ou NUDT15 investigados. Este estudo relatou uma diferença nominal mas não significativa na menor frequência alélica entre as sub-coortes NAT (7,7%) e não-NAT (4,2%) e essa discrepância quantitativa não pode ser explicada pela extensa ancestralidade nativa, uma vez que se analisou sub-coortes com ancestralidade >70% vs. <30% nativa. Deve-se ter um cuidado maior com a população nativa americana para não se extrapolar os dados farmacogenéticos pois nunca se sabe se a pessoa pode ser um portador deum fenótipo metabolizador ruim ou intermediário para TPMT ou NUDT15, evitando-se assim uma possível intoxicaçãopt_BR
dc.publisher.countryBrasilpt_BR
dc.publisher.programPROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS APLICADAS À HEMATOLOGIApt_BR
dc.relation.references1. Kampen KR. The discovery and early understanding of leukemia. Leuk Res [Internet]. 2012;36(1):6–13. Available from: http://dx.doi.org/10.1016/j.leukres.2011.09.028 2. Mehranfar S, Zeinali S, Hosseini R, Mohammadian M, Akbarzadeh A, Feizi AHP. History of Leukemia: Diagnosis and Treatment from beginning to Now. Galen Med J. 2017;6(1):12–22. 3. Farber S, Diamond LK, Mercer RD, Sylvester RF, Wolff JA. Temporary remissions in acute leukemia in children produced by folic acid antagonist, 4- aminopteroyl-glutamic acid. N Engl J Med. 1948;238(23):787–93. 4. Emil F, Emil FJ, Gehan E, Pinkel D, Holland JF, Selawry O, et al. Studies of Sequential and Combination Antimetabolite Therapy in Acute Leukemia: 6- Mercaptopurine and Methotrexate. Blood. 1961;01(01):1–24. 5. Pui C-H, Evans WE. A 50-Year Journey to Cure Childhood Acute Lymphoblastic Leukemia. Semin Hematol [Internet]. 2013 Jul;50(3):185–96. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0037196313000905 6. Secker-Walker LM, Lawler SD, Hardisty RM. Prognostic implications of chromosomal findings in acute lymphoblastic leukaemia at diagnosis. Br Med J. 1978;2(6151):1529–30. 7. Williams DL, Thomas Look A, Melvin SL, Roberson PK, Dahl G, Flake T, et al. New chromosomal translocations correlate with specific immunophenotypes of childhood acute lymphoblastic leukemia. Cell. 1984;36(1):101–9. 8. Yeoh E-J, Ross ME, Shurtleff SA, Williams WK, Patel D, Mahfouz R, et al. Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling. Cancer Cell [Internet]. 2002 Mar;1(2):133–43. Available from: http://www.stjuderesearch. 9. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Vol. 127, Blood. American Society of Hematology; 2016. p. 2391–405. 10. Bennett JM. Changes in the Updated 2016: WHO Classification of the Myelodysplastic Syndromes and Related Myeloid Neoplasms. Clin Lymphoma, Myeloma Leuk. 2016 Nov;16(11):607–9. 11. Estcourt LJ, Bain BJ. WHO Classification of Leukemia [Internet]. Vol. 7, Brenner’s Encyclopedia of Genetics: Second Edition. Elsevier Inc.; 2013. 329–336 p. Available from: http://dx.doi.org/10.1016/B978-0-12-374984-0.01641-7 12. Zhang Y, Rowley JD. Leukemias, Lymphomas, and Other Related Disorders [Internet]. Sixth Edit. Emery and Rimoin’s Principles and Practice of Medical Genetics. Elsevier; 2013. 1–44 p. Available from: http://dx.doi.org/10.1016/B978- 0-12-383834-6.00079-3 13. Society AC. Key Statistics for Acute Lymphocytic Leukemia (ALL) [Internet]. 2020. Available from: https://www.cancer.org/cancer/acute-lymphocytic- leukemia/about/key-statistics.html 14. Cancer Research UK. Acute lymphoblastic leukaemia (ALL) incidence statistics [Internet]. 2017. Available from: https://www.cancerresearchuk.org/health- professional/cancer-statistics/statistics-by-cancer-type/leukaemia- all/incidence#heading-Zero 45 15. Cancer Research UK. Acute lymphoblastic leukaemia (ALL) mortality statistics [Internet]. 2017. Available from: http://www.cancerresearchuk.org/health- professional/cancer-statistics/worldwide-cancer/mortality#heading- Zero%0Ahttp://www.cancerresearchuk.org/health-professional/cancer- statistics/worldwide-cancer/mortality#heading-Zero 16. Oncoguia I. Estatísticas para Leucemia Linfoide Aguda (LLA) [Internet]. 2020. Available from: http://www.oncoguia.org.br/conteudo/estatistica-para-leucemia- linfoide-aguda-lla/7852/316/ 17. Reaman GH. Pediatric oncology: Current views and outcomes. Pediatr Clin North Am. 2002;49(6):1305–18. 18. Gallegos-Arreola MP, Borjas-Gutiérrez C, Zuñiga-Gonzáles GM, Figuera LE, Puebla-Pérez AM, García-González JR. Pathophysiology of Acute Lymphoblastic Leukemia. Vol. 2, Intech open. 2015. 43–73 p. 19. Visvader JE. Cells of origin in cancer. Nature. 2011;469(7330):314–22. 20. Greaves M. Childhood leukaemia. BMJ [Internet]. 2002 Feb 2;324(7332):283–7. Available from: http://www.bmj.com/cgi/doi/10.1136/bmj.324.7332.283 21. Martinelli G, Iacobucci I, Storlazzi CT, Vignetti M, Paoloni F, Cilloni D, et al. IKZF1 (Ikaros) deletions in BCR-ABL1-positive acute lymphoblastic leukemia are associated with short disease-free survival and high rate of cumulative incidence of relapse: A GIMEMA AL WP report. J Clin Oncol. 2009;27(31):5202– 7. 22. Sattlermc M, Griffin JD. Molecular mechanisms of transformation by the BCR- ABL oncogene. Semin Hematol. 2003;40(2):4–10. 23. Meenaghan T, Dowling M, Kelly M. Acute leukaemia: Making sense of a complex blood cancer. Br J Nurs. 2012 Jan;21(2):76–83. 24. Advani A. Acute lymphoblastic leukemia (ALL). Vol. 30, Best Practice and Research: Clinical Haematology. Bailliere Tindall Ltd; 2017. p. 173–4. 25. Rafei H, Kantarjian HM, Jabbour EJ. Recent advances in the treatment of acute lymphoblastic leukemia. Leuk Lymphoma [Internet]. 2019;0(0):1–16. Available from: https://doi.org/10.1080/10428194.2019.1605071 26. Monteiro LC. Avaliação da Prevalência e Suscetibilidade Antifúngica de Candida Isoladas da Cavidade Bucal de Pacientes Infanto-Juvenis com Leucemia Linfocítica Aguda [Internet]. Universidade Federal da Paraíba; 2015 [cited 2018 Apr 16]. Available from: http://tede.biblioteca.ufpb.br/bitstream/tede/8871/2/arquivototal.pdf 27. Rocha JMC, Xavier SG, de Lima Souza ME, Assumpção JG, Murao M, de Oliveira BM. Current strategies for the detection of minimal residual disease in childhood acute lymphoblastic leukemia. Mediterr J Hematol Infect Dis. 2016;8(1). 28. Costa S de S, Silva A de M, Macedo I de AB. Conhecimento De Manifestações Orais Da Leucemia e Protocolos de Atendimento Odontológico. Revista de Odontologia da Universidade Cidade de São Paulo. 2011;23(1):70–8. 29. Maia R da RP, Filho VW. Infection and childhood leukemia : review of evidence. Rev Saúde Pública. 2013;47(6):1172–85. 30. Master S, Koshy N, Mansour R, Shi R. Effect of Stem Cell Transplant on Survival in Adult Patients With Acute Lymphoblastic Leukemia : NCDB Analysis. Anticancer Res. 2019;1906(39):1899–906. 31. Schmiegelow K, Vestergaard T, Nielsen SM, Hjalgrim H. Etiology of common childhood acute lymphoblastic leukemia: The adrenal hypothesis. Leukemia. 2008;22(12):2137–41. 46 32. Greaves MF, Wiemels J. Origins of chromosome translocations in childhood leukaemia. Nat Rev Cancer. 2003;3(9):639–49. 33. Pavlovic S, Kotur N, Stankovic B, Zukic B, Gasic V, Dokmanovic L. Pharmacogenomic and pharmacotranscriptomic profiling of childhood acute lymphoblastic leukemia: Paving the way to personalized treatment. Genes (Basel). 2019;10(3). 34. Rocha BC. Leucemia Linfóide Aguda - Relato de um Caso e Revisão de Literatura. São Paulo; 2012. (1). Report No.: 1. 35. Pui CH, Gaynon PS, Boyett JM, Chessells JM, Baruchel A, Kamps W, et al. Outcome of treatment in childhood acute lymphoblastic leukaemia with rearrangements of the 11q23 chromosomal region. Lancet. 2002 Jun;359(9321):1909–15. 36. Pedrosa F. Leucemia linfóide aguda : uma doença curável Acute lymphoblastic leukemia : a curable disease. 2002;2(1):63–8. 37. Rudin S, Marable M, Huang RS. The Promise of Pharmacogenomics in Reducing Toxicity During Acute Lymphoblastic Leukemia Maintenance Treatment. Genomics Proteomics Bioinformatics [Internet]. 2017 Apr;15(2):82–93. Available from: http://dx.doi.org/10.1016/j.gpb.2016.11.003 38. Möricke A, Zimmermann M, Valsecchi MG, Stanulla M, Biondi A, Mann G, et al. Dexamethasone vs prednisone in induction treatment of pediatric ALL: results of the randomized trial AIEOP-BFM ALL 2000. Blood. 2016;127(17):2101–12. 39. Vande Voorde J, Quintiliani M, McGuigan C, Liekens S, Balzarini J. Inhibition of pyrimidine and purine nucleoside phosphorylases by a 3,5-dichlorobenzoyl- substituted 2-deoxy-d-ribose-1-phosphate derivative. Biochem Pharmacol. 2012 May;83(10):1358–63. 40. Robak P, Robak T. Older and new purine nucleoside analogs for patients with acute leukemias. Vol. 39, Cancer Treatment Reviews. 2013. p. 851–61. 41. Rang HP, Dale MM, Ritter JM, Moore PK. Farmacologia. 5 a . London; 2003. 1– 914 p. 42. Daehn I, Brem R, Barkauskaite E, Karran P. 6-Thioguanine damages mitochondrial DNA and causes mitochondrial dysfunction in human cells. FEBS Lett. 2011 Dec;585(24):3941–6. 43. Yates CR, Krynetski EY, Loennechen T, Fessing MY, Tai H, Pui C, et al. Molecular Diagnosis of Thiopurine S-Methyltransferase Deficiency: Genetic Basis for Azathioprine and Mercaptopurine Intolerance. Ann Intern Med [Internet]. 1997;126(8):1–7. Available from: papers3://publication/uuid/FC367CD6-84E2- 4751-8579-CD3C94D2E445 44. Ailing Z, Jing Y, Jingli L, Yun X, Xiaojian Z. Further evidence that a variant of the gene NUDT15 may be an important predictor of azathioprine-induced toxicity in Chinese subjects: a case report. J Clin Pharm Ther. 2016;41(5):572–4. 45. Pacheco Neto M, Alves ANL, Fortini AS, Burattini M do N, Sumita NM, Srougi M, et al. Monitoração terapêutica da azatioprina: uma revisão. J Bras Patol e Med Lab. 2008;44(3):161–7. 46. Weinshilboum R. Inheritance and Drug Response. N Engl J Med [Internet]. 2003;348(6):529–37. Available from: http://www.nejm.org/doi/10.1056/NEJMra020021 47. Ford LT, Berg JD. Thiopurine S-methyltransferase (TPMT) assessment prior to starting thiopurine drug treatment; a pharmacogenomic test whose time has come. J Clin Pathol [Internet]. 2010 Apr 1 [cited 2019 Feb 15];63(4):288–95. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20354201 47 48. Wang R, Liu B, Li J, Xu J, Wang X, Zhao Z, et al. Association between the c.415C > T, c.52G > A, and 36_37insGGAGTC polymorphisms of NUDT 15 and thiopurine-induced leukopenia, thiopurine intolerance, and severe hair loss: an updated meta-analysis. Drug Des Devel Ther [Internet]. 2019 Aug;Volume 13:2729–44. Available from: https://www.dovepress.com/association-between- the-c415c-gt-t-c52g-gt-a-and-3637insggagtc-polymor-peer-reviewed-article- DDDT 49. Lennard L. The clinical pharmacology of 6-mercaptopurine. Eur J Clin Pharmacol. 1992;43(1):329–39. 50. Brouwer C, De Abreu RA, Keizer-Garritsen JJ, Lambooy LHJ, Ament K, Ter Riet PGJH, et al. Thiopurine methyltransferase in acute lymphoblastic leukaemia: Biochemical and molecular biological aspects. Eur J Cancer. 2005;41(4):613–23. 51. Paugh SW, Stocco G, Evans WE. Pharmacogenomics in pediatric leukemia. Curr Opin Pediatr. 2010;22(6):703–10. 52. Zhou S. Clinical Pharmacogenomics of Thiopurine S-methyltransferase. Curr Clin Pharmacol. 2013;1(1):119–28. 53. Mei L, Ontiveros EP, Griffiths EA, Thompson JE, Wang ES, Wetzler M. Pharmacogenetics predictive of response and toxicity in acute lymphoblastic leukemia therapy. Blood Rev. 2015;29(4):243–9. 54. 2018_Relling, M. V., et. al. - Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for thiopurine dosing based on TPMT and NUDT15 genotypes - 2018 update.pdf. 55. Yang JJ, Whirl-Carrillo M, Scott SA, Turner AJ, Schwab M, Tanaka Y, et al. Pharmacogene Variation Consortium Gene Introduction: NUDT15. Clin Pharmacol Ther [Internet]. 2018 [cited 2019 Feb 15];0(0):1–4. Available from: http://doi.wiley.com/10.1002/cpt.1268 56. Moriyama T, Nishii R, Ting-Nien L, Kihira K, Toyoda H, Nersting J, et al. The Effects of Inherited NUDT15 Polymorphisms on Thiopurine Active Metabolites in Japanese Children with Acute Lymphoblastic Leukemia. Pharmacogenet Genomics. 2015;27(4):215–25. 57. Yang JJ, Landier W, Yang W, Liu C, Hageman L, Cheng C, et al. Inherited NUDT15 variant is a genetic determinant of mercaptopurine intolerance in children with acute lymphoblastic leukemia. J Clin Oncol. 2015;33(11):1235–42. 58. Eichelbaum M, Ingelman-Sundberg M, Evans WE. Pharmacogenomics and Individualized Drug Therapy. Annu Rev Med. 2006;57(1):119–37. 59. Metzger IF, Souza-Costa DC, Tanus-Santos JE. FARMACOGENÉTICA: PRINCÍPIOS , APLICAÇÕES E PERSPECTIVAS*. In: Simpósio: Farmacogenética. 2006. p. 515–21. 60. Reis M. Farmacogenética Aplicada Ao Câncer. Quimioterapia Individualizada E Especificidade Molecular. Simpósio Farm. 2006;39(4):577. 61. Lennard L, Lilleyman JS, Van Loon J, Weinshilboum RM. Genetic variation in response to 6-mercaptopurine for childhood acute lymphoblastic leukaemia. Lancet. 1990;336(8709):225–9. 62. Relling M V., Schwab M, Whirl-Carrillo M, Suarez-Kurtz G, Pui CH, Stein CM, et al. Clinical Pharmacogenetics Implementation Consortium Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2018 Update. Clin Pharmacol Ther. 2019;105(5):1095–105. 63. ANSARI A, HASSAN C, DULEY J, MARINAKI A, SHOBOWALE-BAKRE E, SEED P, et al. Thiopurine methyltransferase activity and the use of azathioprine in inflammatory bowel disease. Aliment Pharmacol Ther. 2002;16(10):1743–50. 48 64. Otterness D, Szumlanski C, Lennard L, Klemetsdal B, Aarbakke J, Park-Hah JO, et al. Human thiopurine methyltransferase pharmacogenetics: Gene sequence polymorphisms. Clin Pharmacol Ther. 1997;62(1):60–73. 65. Schaeffeler E, Stanulla M, Greil J, Schrappe M, Eichelbaum M, Zanger UM, et al. A novel TPMT missense mutation associated with TPMT deficiency in a 5-year- old boy with all [6]. Leukemia. 2003;17(7):1422–4. 66. Schaeffeler E, Lang T, Zanger UM, Eichelbaum M, Schwab M. High-thoughput genotyping of thiopurine s-methyltransferase by denaturing hplc. Clin Chem. 2001;47(3):548–55. 67. Collie-Duguid ESR, Pritchard, Powrie, Sludden J, Collier, Li T, et al. The frequency and distribution of thiopurine methyltransferase alleles in Caucasian and Asian populations. Pharmacogenetics [Internet]. 1999 Feb;9(1):37–42. Available from: https://insights.ovid.com/crossref?an=00008571-199902000-00006 68. Relling M V., Gardner EE, Sandborn WJ, Schmiegelow K, Pui CH, Yee SW, et al. Clinical pharmacogenetics implementation consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing: 2013 update. Clin Pharmacol Ther. 2013;93(4):324–5. 69. Sanderson J, Ansari A, Marinaki T, Duley J. Thiopurine methyltransferase: Should it be measured before commencing thiopurine drug therapy? Ann Clin Biochem. 2004;41(4):294–302. 70. Yin D, Xia X, Zhang J, Zhang S, Liao F, Zhang G, et al. Impact of NUDT15 polymorphisms on thiopurines-induced myelotoxicity and thiopurines tolerance dose. Oncotarget [Internet]. 2017 Feb 21;8(8):13575–85. Available from: http://www.oncotarget.com/fulltext/14594 71. Zhang AL, Yang J, Wang H, Lu JL, Tang S, Zhang XJ. Association of NUDT15 c.415C>T allele and thiopurine-induced leukocytopenia in Asians: a systematic review and meta-analysis. Ir J Med Sci. 2018;187(1):145–53. 72. Suarez-kurtz G, Brisson GD, Hutz MH, Petzl-erler L, Salzano FM. Letter to the Editor NUDT15 polymorphism in Native American populations of Brazil Authors Coordenação de Pesquisa , Instituto Nacional de Câncer , Rio de Janeiro , Brazil Departamento de Genética , Universidade Federal do Rio Grande do Sul , Porto Alegre . :1–5. 73. Nolan T, Huggett J, Sanchez E. Good Practice Guide for the Application of Quantitative PCR (qPCR). Natl Meas Syst. 2013;50. 74. Park Y, Kim H, Choi JY, Yun S, Min BJ, Seo ME, et al. Star Allele-Based Haplotyping versus Gene-Wise Variant Burden Scoring for Predicting 6- Mercaptopurine Intolerance in Pediatric Acute Lymphoblastic Leukemia Patients. Front Pharmacol. 2019;10(JUN):1–10. 75. Paschou P, Lewis J, Javed A, Drineas P. Ancestry informative markers for fine- scale individual assignment to worldwide populations. J Med Genet. 2010;47(12):835–47. 76. Rosenberg NA, Li LM, Ward R, Pritchard JK. Informativeness of Genetic Markers for Inference of Ancestry. Am J Hum Genet. 2003;73(6):1402–22.pt_BR
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