scholarly journals TPMT*3C as a Predictor of 6-Mercaptopurine-Induced Myelotoxicity in Thai Children with Acute Lymphoblastic Leukemia

2021 ◽  
Vol 11 (8) ◽  
pp. 783
Author(s):  
Thawinee Jantararoungtong ◽  
Supaporn Wiwattanakul ◽  
Rawiporn Tiyasirichokchai ◽  
Santirhat Prommas ◽  
Rattanaporn Sukprasong ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Genetic Polymorphisms ◽  
Lymphoblastic Leukemia ◽  
Drug Transporters ◽  
Severe Neutropenia ◽  
Drug Metabolizing Enzymes ◽  
Wild Type ◽  
Metabolizing Enzymes ◽  
Increased Risk ◽  
Genes Encoding

The response to 6-mercaptopurine (6-MP) can be altered by genetic polymorphisms in genes encoding drug-metabolizing enzymes and drug transporters. The purpose of this study was to investigate the association between genetic polymorphisms of drug-metabolizing enzymes (TPMT 719A > G (*3C), ITPA 94C > A and ITPA 123G > A) and drug transporters (MRP4 912C > A and MRP4 2269G > A) with 6-MP-related myelotoxicity and hepatotoxicity in Thai children with acute lymphoblastic leukemia (ALL). The prescribed dosage of 6-MP and its adverse effects were assessed from medical records during the first 8 weeks and 9–24 weeks of maintenance therapy. Children with the TPMT*1/*3C genotype had a higher risk of leukopenia with an odds ratio (OR) of 4.10 (95% confidence interval (CI) of 1.06–15.94; p = 0.033) compared to wild type (TPMT*1/*1) patients. Heterozygous TPMT*3C was significantly associated with severe neutropenia with an increased risk (OR, 4.17; 95% CI, 1.25–13.90); p = 0.014) during the first 8 weeks. No association was found among ITPA94C > A, ITPA123G > A, MRP4 912C > A, and MRP4 2269G > A with myelotoxicity and hepatotoxicity. The evidence that TPMT heterozygotes confer risks of 6-MP-induced myelotoxicity also supports the convincing need to genotype this pharmacogenetic marker before the initiation of 6-MP therapy.

scholarly journals Genetic Polymorphisms of Drug-Metabolizing Enzymes Involved in 6-Mercaptopurine-Induced Myelosuppression in Thai Pediatric Acute Lymphoblastic Leukemia Patients

2020 ◽  
Author(s):  
Kanyarat Khaeso ◽  
Nontaya Nakkam ◽  
Patcharee Komwilaisak ◽  
Piyathida Wongmast ◽  
Su-on Chainansamit ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Dna Sequencing ◽  
Allele Frequency ◽  
Genetic Polymorphisms ◽  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
Drug Metabolizing Enzymes ◽  
Metabolizing Enzymes ◽  
Pediatric Acute Lymphoblastic Leukemia ◽  
Pediatric All

AbstractGenetic polymorphisms of thiopurine S-methyltransferase (TPMT) and nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) genes have been proposed as key determinants of 6-mercaptopurine (6-MP)-induced myelosuppression in pediatric acute lymphoblastic leukemia (ALL). In the present study, genotypes of TPMT and NUDT15 were investigated in 178 Thai pediatric patients with ALL by the TaqMan SNP genotyping assay and DNA sequencing. The frequency of TPMT*3C was 0.034. Among NUDT15 variants, NUDT15*3 is the most common variant with the allele frequency of 0.073, whereas those of NUDT15*2, NUDT15*5, and NUDT15*6 variants were 0.022, 0.011, and 0.039. These data suggest that a high proportion of Thai pediatric ALL patients may be at risk of thiopurine-induced myelosuppression.

scholarly journals Genetic Polymorphisms Associated to Folate Transport as Predictors of Increased Risk for Acute Lymphoblastic Leukemia in Mexican Children

2016 ◽  
Vol 7 ◽  
Author(s):  
Fausto Zaruma-Torres ◽  
Ismael Lares-Asseff ◽  
Aurea Lima ◽  
Aarón Reyes-Espinoza ◽  
Verónica Loera-Castañeda ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Genetic Polymorphisms ◽  
Lymphoblastic Leukemia ◽  
Folate Transport ◽  
Mexican Children ◽  
Increased Risk

scholarly journals Polymorphisms of drug-metabolizing enzymes and risk of childhood acute lymphoblastic leukemia

2005 ◽  
Vol 79 (3) ◽  
pp. 202-205 ◽  
Author(s):  
S. Pakakasama ◽  
E. Mukda ◽  
W. Sasanakul ◽  
P. Kadegasem ◽  
U. Udomsubpayakul ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Drug Metabolizing Enzymes ◽  
Metabolizing Enzymes

scholarly journals Pharmacogenetics of drug-metabolizing enzymes in Italian populations

2015 ◽  
Vol 30 (2) ◽  
Author(s):  
Loredana Serpe ◽  
Roberto Canaparo ◽  
Maria Gabriella Scordo ◽  
Edoardo Spina
Keyword(s):  
Drug Metabolism ◽  
Genetic Polymorphisms ◽  
Drug Prescription ◽  
The Body ◽  
Published Data ◽  
Drug Metabolizing Enzymes ◽  
Metabolizing Enzymes ◽  
Racial Origin ◽  
Genes Encoding ◽  
Subsequent Elimination

AbstractDrug-metabolizing enzymes play a major role in the biotransformation and subsequent elimination of most drugs and xenobiotics from the body. Both phase I and phase II enzymes are highly polymorphic. Inter-individual differences in genes coding for drug-metabolizing enzymes are important for understanding variability in drug response and for individualization of drug prescription. The prevalence of genetic polymorphisms in drug metabolism varies widely with ethnicity, and marked differences in the distribution of allelic variants of genes encoding drug-metabolizing enzymes have been documented in populations of different racial origin. This review aimed to summarize the available studies on genetic polymorphisms associated with drug metabolism conducted in Italian populations and to compare the frequency of the various metabolizer phenotypes and most common variant alleles (and resulting genotypes) with corresponding values from other populations. Notably, published data are not extensive, and most studies were performed on relatively low numbers of individuals. In general, the frequency of polymorphisms in the cytochrome P450 (

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