Cargando…
Pharmacogenetic Analysis of Pediatric Patients with Acute Lymphoblastic Leukemia: A Possible Association between Survival Rate and ITPA Polymorphism
Genetic polymorphisms are important factors in the effects and toxicity of chemotherapeutics. To analyze the pharmacogenetic and ethnic differences in chemotherapeutics, major genes implicated in the treatment of acute lymphoblastic leukemia (ALL) were analyzed. Eighteen loci of 16 genes in 100 pati...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3454425/ https://www.ncbi.nlm.nih.gov/pubmed/23029095 http://dx.doi.org/10.1371/journal.pone.0045558 |
_version_ | 1782244503009099776 |
---|---|
author | Kim, Hyery Kang, Hyoung Jin Kim, Hyo Jeong Jang, Mi Kyung Kim, Nam Hee Oh, Yongtaek Han, Byoung-Don Choi, Ji-Yeob Kim, Chul Woo Lee, Ji Won Park, Kyung Duk Shin, Hee Young Ahn, Hyo Seop |
author_facet | Kim, Hyery Kang, Hyoung Jin Kim, Hyo Jeong Jang, Mi Kyung Kim, Nam Hee Oh, Yongtaek Han, Byoung-Don Choi, Ji-Yeob Kim, Chul Woo Lee, Ji Won Park, Kyung Duk Shin, Hee Young Ahn, Hyo Seop |
author_sort | Kim, Hyery |
collection | PubMed |
description | Genetic polymorphisms are important factors in the effects and toxicity of chemotherapeutics. To analyze the pharmacogenetic and ethnic differences in chemotherapeutics, major genes implicated in the treatment of acute lymphoblastic leukemia (ALL) were analyzed. Eighteen loci of 16 genes in 100 patients with ALL were analyzed. The distribution of variant alleles were CYP3A4*1B (0%), CYP3A5*3 (0%), GSTM1 (21%), GSTP1 (21%), GSTT1 (16%), MDR1 exon 21 (77%), MDR1 exon 26 (61%), MTHFR 677 (63%), MTHFR 1298 (29%), NR3C1 1088 (0%), RFC1 80 (68%), TPMT combined genotype (7%), VDR intron 8 (11%), VDR FokI (83%), TYMS enhancer repeat (22%) and ITPA 94 (30%). The frequencies of single nucleotide polymorphisms (SNPs) of 10 loci were statistically different from those in Western Caucasians. Dose percents (actual/planned dose) or toxicity of mercaptopurine and methotrexate were not related to any SNPs. Event free survival (EFS) rate was lower in ITPA variants, and ITPA 94 AC/AA variant genotypes were the only independent risk factor for lower EFS in multivariate analysis, which was a different pharmacogenetic implication from Western studies. This study is the first pharmacogenetic study in Korean pediatric ALL. Our result suggests that there are other possible pharmacogenetic factors besides TPMT or ITPA polymorphisms which influence the metabolism of mercaptopurine in Asian populations. |
format | Online Article Text |
id | pubmed-3454425 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34544252012-10-01 Pharmacogenetic Analysis of Pediatric Patients with Acute Lymphoblastic Leukemia: A Possible Association between Survival Rate and ITPA Polymorphism Kim, Hyery Kang, Hyoung Jin Kim, Hyo Jeong Jang, Mi Kyung Kim, Nam Hee Oh, Yongtaek Han, Byoung-Don Choi, Ji-Yeob Kim, Chul Woo Lee, Ji Won Park, Kyung Duk Shin, Hee Young Ahn, Hyo Seop PLoS One Research Article Genetic polymorphisms are important factors in the effects and toxicity of chemotherapeutics. To analyze the pharmacogenetic and ethnic differences in chemotherapeutics, major genes implicated in the treatment of acute lymphoblastic leukemia (ALL) were analyzed. Eighteen loci of 16 genes in 100 patients with ALL were analyzed. The distribution of variant alleles were CYP3A4*1B (0%), CYP3A5*3 (0%), GSTM1 (21%), GSTP1 (21%), GSTT1 (16%), MDR1 exon 21 (77%), MDR1 exon 26 (61%), MTHFR 677 (63%), MTHFR 1298 (29%), NR3C1 1088 (0%), RFC1 80 (68%), TPMT combined genotype (7%), VDR intron 8 (11%), VDR FokI (83%), TYMS enhancer repeat (22%) and ITPA 94 (30%). The frequencies of single nucleotide polymorphisms (SNPs) of 10 loci were statistically different from those in Western Caucasians. Dose percents (actual/planned dose) or toxicity of mercaptopurine and methotrexate were not related to any SNPs. Event free survival (EFS) rate was lower in ITPA variants, and ITPA 94 AC/AA variant genotypes were the only independent risk factor for lower EFS in multivariate analysis, which was a different pharmacogenetic implication from Western studies. This study is the first pharmacogenetic study in Korean pediatric ALL. Our result suggests that there are other possible pharmacogenetic factors besides TPMT or ITPA polymorphisms which influence the metabolism of mercaptopurine in Asian populations. Public Library of Science 2012-09-24 /pmc/articles/PMC3454425/ /pubmed/23029095 http://dx.doi.org/10.1371/journal.pone.0045558 Text en © 2012 Kim et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Kim, Hyery Kang, Hyoung Jin Kim, Hyo Jeong Jang, Mi Kyung Kim, Nam Hee Oh, Yongtaek Han, Byoung-Don Choi, Ji-Yeob Kim, Chul Woo Lee, Ji Won Park, Kyung Duk Shin, Hee Young Ahn, Hyo Seop Pharmacogenetic Analysis of Pediatric Patients with Acute Lymphoblastic Leukemia: A Possible Association between Survival Rate and ITPA Polymorphism |
title | Pharmacogenetic Analysis of Pediatric Patients with Acute Lymphoblastic Leukemia: A Possible Association between Survival Rate and ITPA Polymorphism |
title_full | Pharmacogenetic Analysis of Pediatric Patients with Acute Lymphoblastic Leukemia: A Possible Association between Survival Rate and ITPA Polymorphism |
title_fullStr | Pharmacogenetic Analysis of Pediatric Patients with Acute Lymphoblastic Leukemia: A Possible Association between Survival Rate and ITPA Polymorphism |
title_full_unstemmed | Pharmacogenetic Analysis of Pediatric Patients with Acute Lymphoblastic Leukemia: A Possible Association between Survival Rate and ITPA Polymorphism |
title_short | Pharmacogenetic Analysis of Pediatric Patients with Acute Lymphoblastic Leukemia: A Possible Association between Survival Rate and ITPA Polymorphism |
title_sort | pharmacogenetic analysis of pediatric patients with acute lymphoblastic leukemia: a possible association between survival rate and itpa polymorphism |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3454425/ https://www.ncbi.nlm.nih.gov/pubmed/23029095 http://dx.doi.org/10.1371/journal.pone.0045558 |
work_keys_str_mv | AT kimhyery pharmacogeneticanalysisofpediatricpatientswithacutelymphoblasticleukemiaapossibleassociationbetweensurvivalrateanditpapolymorphism AT kanghyoungjin pharmacogeneticanalysisofpediatricpatientswithacutelymphoblasticleukemiaapossibleassociationbetweensurvivalrateanditpapolymorphism AT kimhyojeong pharmacogeneticanalysisofpediatricpatientswithacutelymphoblasticleukemiaapossibleassociationbetweensurvivalrateanditpapolymorphism AT jangmikyung pharmacogeneticanalysisofpediatricpatientswithacutelymphoblasticleukemiaapossibleassociationbetweensurvivalrateanditpapolymorphism AT kimnamhee pharmacogeneticanalysisofpediatricpatientswithacutelymphoblasticleukemiaapossibleassociationbetweensurvivalrateanditpapolymorphism AT ohyongtaek pharmacogeneticanalysisofpediatricpatientswithacutelymphoblasticleukemiaapossibleassociationbetweensurvivalrateanditpapolymorphism AT hanbyoungdon pharmacogeneticanalysisofpediatricpatientswithacutelymphoblasticleukemiaapossibleassociationbetweensurvivalrateanditpapolymorphism AT choijiyeob pharmacogeneticanalysisofpediatricpatientswithacutelymphoblasticleukemiaapossibleassociationbetweensurvivalrateanditpapolymorphism AT kimchulwoo pharmacogeneticanalysisofpediatricpatientswithacutelymphoblasticleukemiaapossibleassociationbetweensurvivalrateanditpapolymorphism AT leejiwon pharmacogeneticanalysisofpediatricpatientswithacutelymphoblasticleukemiaapossibleassociationbetweensurvivalrateanditpapolymorphism AT parkkyungduk pharmacogeneticanalysisofpediatricpatientswithacutelymphoblasticleukemiaapossibleassociationbetweensurvivalrateanditpapolymorphism AT shinheeyoung pharmacogeneticanalysisofpediatricpatientswithacutelymphoblasticleukemiaapossibleassociationbetweensurvivalrateanditpapolymorphism AT ahnhyoseop pharmacogeneticanalysisofpediatricpatientswithacutelymphoblasticleukemiaapossibleassociationbetweensurvivalrateanditpapolymorphism |