ArticleEuropean journal of clinical pharmacology2004
Phenotype and genotype for thiopurine methyltransferase activity in the French Caucasian population: impact of age.
Article in European journal of clinical pharmacology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 82 citations in OpenAlex.
- Thiopurine S-methyltransferase testing for averting drug toxicity: a meta-analysis of diagnostic test accuracy.The pharmacogenomics journal · 2016Pooled it
- Thiopurine S-methyltransferase testing for averting drug toxicity in patients receiving thiopurines: a systematic review.Pharmacogenomics · 2016Pooled it
- Article
- Pharmacogenetic studies of thiopurine methyltransferase genotype-phenotype concordance and effect of methotrexate on thiopurine metabolism.Basic & clinical pharmacology & toxicology · 2021Review
- Ontogeny of Drug-Metabolizing Enzymes.Methods in molecular biology (Clifton, N.J.) · 2021Review
- Modeling the Outcome of Systematic TPMT Genotyping or Phenotyping Before Azathioprine Prescription: A Cost-Effectiveness Analysis.Molecular diagnosis & therapy · 2019Article
- Genetic Polymorphism of Thiopurine S-methyltransferase in Children with Acute Lymphoblastic Leukemia in JordanAsian Pacific journal of cancer prevention : APJCP · 2018Article
- Thiopurine S-Methyltransferase as a Pharmacogenetic Biomarker: Significance of Testing and Review of Major Methods.Cardiovascular & hematological agents in medicinal chemistry · 2017Review
- Genomewide Approach Validates Thiopurine Methyltransferase Activity Is a Monogenic Pharmacogenomic Trait.Clinical pharmacology and therapeutics · 2017Article
- Pharmacogenomics in Pediatric Oncology: Review of Gene-Drug Associations for Clinical Use.International journal of molecular sciences · 2016Review
- Polymorphisms of the thiopurine S-methyltransferase gene among the Libyan population.The Libyan journal of medicine · 2015Article
- Frequency of thiopurine S-methyltransferase mutant alleles in indigenous and admixed Guatemalan patients with acute lymphoblastic leukemia.Medical oncology (Northwood, London, England) · 2013Article
- Gene polymorphisms involved in manifestation of leucopenia, digestive intolerance, and pancreatitis in azathioprine-treated patients.Digestive diseases and sciences · 2012Article
- Pharmacogenetic determinants of mercaptopurine disposition in children with acute lymphoblastic leukemia.European journal of clinical pharmacology · 2012Review
- Article
- Optimization of conventional therapy in patients with IBD.Nature reviews. Gastroenterology & hepatology · 2011Review
- Frequency of TPMT alleles in Indian patients with acute lymphatic leukemia and effect on the dose of 6-mercaptopurine.Medical oncology (Northwood, London, England) · 2010Article
- Identifying genomic and developmental causes of adverse drug reactions in children.Pharmacogenomics · 2010Review
- Genetic analysis of thiopurine methyltransferase polymorphism in the Jordanian population.European journal of clinical pharmacology · 2010Article
- Thiopurine S-methyltransferase alleles, TPMT(*)2, (*)3B and (*)3C, and genotype frequencies in an Indian population.Experimental and therapeutic medicine · 2010Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThiopurine drugs are commonly used in pediatric patients for the treatment of acute leukemia, organ transplantation and inflammatory diseases. They are catabolized by the cytosolic thiopurine methyltransferase (TPMT), which is subject to a genetic polymorphism. In children, enzyme activities are immature at birth and developmental patterns vary widely from one enzyme to another. The present study was undertaken to evaluate erythrocyte TPMT activity and the correlation between genotype and phenotype in different age groups from birth to adolescence and adulthood.
methodsThe study included 304 healthy adult blood donors, 147 children and 18 neonates (cord bloods). TPMT activity was measured by liquid chromatography, and genotype was determined using a polymerase chain reaction reverse dot-blot analysis identifying the predominant TPMT mutant alleles (TPMT*3A, TPMT*3B, TPMT*3C, TPMT*2).
resultsThere was no significant difference in TPMT activity between cord bloods ( n=18) and children ( n=147) (17.48+/-4.04 versus 18.62+/-4.14 respectively, P=0.424). However, TPMT was significantly lower in children than in adults (19.34+/-4.09) ( P=0.033). In the whole population, there were 91.9% homozygous wild type, 7.9% heterozygous mutants and 0.2% homozygous mutants. The frequency of mutant alleles was 3.0% for TPMT*3A, 0.7% for TPMT*2 and 0.4% for TPMT*3C.
conclusionNo impact of child development on TPMT activity could be evidenced, suggesting that TPMT activity is already mature at birth. The difference between children and adults was low with reduced clinical impact expected. When individual TPMT activity was compared with genotype, there was an overlapping region where subjects (4.5%, 12 adults, 9 children) were either homozygous wild type or heterozygous, with a TPMT activity below the antimode value. This result highlighted the importance of measuring TPMT activity to detect all patients at risk of thiopurine toxicity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.