NUDT15 gene polymorphism related to mercaptopurine intolerance in Taiwan Chinese children with acute lymphoblastic leukemia.

Liang, D-C; Yang, C-P; Liu, H-C; Jaing, T-H; Chen, S-H; Hung, I-J; Yeh, T-C; Lin, T-H; Lai, C-L; Lai, C-Y; Shih, L-Y

Liang, D-C; Yang, C-P; Liu, H-C; Jaing, T-H; Chen, S-H; Hung, I-J; Yeh, T-C; Lin, T-H; Lai, C-L; Lai, C-Y; Shih, L-Y.

Afiliación

Liang DC; Division of Pediatric Hematology-Oncology, Mackay Children's Hospital and Mackay Medical College, Taipei, Taiwan.
Yang CP; Division of Pediatric Hematology-Oncology, Chang Gung Children's Hospital, Taoyuan, Taiwan.
Liu HC; Division of Pediatric Hematology-Oncology, Mackay Children's Hospital and Mackay Medical College, Taipei, Taiwan.
Jaing TH; Division of Pediatric Hematology-Oncology, Chang Gung Children's Hospital, Taoyuan, Taiwan.
Chen SH; Chang Gung University, Taoyuan, Taiwan.
Hung IJ; Division of Pediatric Hematology-Oncology, Chang Gung Children's Hospital, Taoyuan, Taiwan.
Yeh TC; Chang Gung University, Taoyuan, Taiwan.
Lin TH; Division of Pediatric Hematology-Oncology, Chang Gung Children's Hospital, Taoyuan, Taiwan.
Lai CL; Division of Pediatric Hematology-Oncology, Mackay Children's Hospital and Mackay Medical College, Taipei, Taiwan.
Lai CY; Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.
Shih LY; Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.

Pharmacogenomics J ; 16(6): 536-539, 2016 11.

Article en En | MEDLINE | ID: mdl-26503813

RESUMEN

A recent study identified a variant of the NUDT15 gene (rs116855232 C>T) associated with intolerance to thiopurine in Korean patients with Crohn's disease. This study prompted us to substantiate the finding in a Taiwanese population. Four hundred and four children with acute lymphoblastic leukemia (ALL), and 100 adults with chronic immune thrombocytopenic purpura or localized lymphoma having normal bone marrow were examined. Two candidate gene approaches, pyrosequencing for NUDT15 and TaqMan assay for thiopurine methyltransferase (TPMT) genotyping (rs1142345 A>G), were performed. We showed a risk allele frequency of NUDT15 of 11.6% in children with ALL and 15.5% in adults. By contrast, the risk allele frequency of TPMT was only 1.6% in children with ALL and 0.5% in adults. The high frequency of risk variant for NUDT15, but not the very low frequency of risk variant for TPMT, was closely associated with the intolerance to mercaptopurine in children with ALL in Taiwan, contrast to that of European descent. In regard to NUDT15 polymorphism, the maximal tolerable daily doses of mercaptopurine in homozygotes, heterozygotes and wild-type groups were 9.4 mg m-2, 30.7 mg m-2 and 44.1 mg m-2, respectively. The outcomes did not differ significantly among the different genotypes.

Asunto(s)

Antimetabolitos Antineoplásicos/efectos adversos; Mercaptopurina/efectos adversos; Variantes Farmacogenómicas; Polimorfismo Genético; Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico; Pirofosfatasas/genética; Factores de Edad; Antimetabolitos Antineoplásicos/administración & dosificación; Niño; Preescolar; Supervivencia sin Enfermedad; Femenino; Frecuencia de los Genes; Estudios de Asociación Genética; Heterocigoto; Homocigoto; Humanos; Lactante; Recién Nacido; Estimación de Kaplan-Meier; Masculino; Dosis Máxima Tolerada; Mercaptopurina/administración & dosificación; Farmacogenética; Pruebas de Farmacogenómica/métodos; Fenotipo; Reacción en Cadena de la Polimerasa; Medicina de Precisión; Leucemia-Linfoma Linfoblástico de Células Precursoras/enzimología; Leucemia-Linfoma Linfoblástico de Células Precursoras/genética; Valor Predictivo de las Pruebas; Pirofosfatasas/metabolismo; Factores de Riesgo; Taiwán; Factores de Tiempo; Resultado del Tratamiento

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polimorfismo Genético / Pirofosfatasas / Leucemia-Linfoma Linfoblástico de Células Precursoras / Variantes Farmacogenómicas / Mercaptopurina / Antimetabolitos Antineoplásicos Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Child / Child, preschool / Female / Humans / Infant / Male / Newborn País/Región como asunto: Asia Idioma: En Revista: Pharmacogenomics J Asunto de la revista: BIOLOGIA MOLECULAR / FARMACOLOGIA Año: 2016 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Estados Unidos

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