title: Thiopurine S-methyltransferase testing for averting drug toxicity: a meta-analysis of diagnostic test accuracy.
abstract: Thiopurine S-methyltransferase (TPMT) deficiency increases the risk of serious adverse events in persons receiving thiopurines. The objective was to synthesize reported sensitivity and specificity of TPMT phenotyping and genotyping using a latent class hierarchical summary receiver operating characteristic meta-analysis. In 27 studies, pooled sensitivity and specificity of phenotyping for deficient individuals was 75.9% (95% credible interval (CrI), 58.3-87.0%) and 98.9% (96.3-100%), respectively. For genotype tests evaluating TPMT*2 and TPMT*3, sensitivity and specificity was 90.4% (79.1-99.4%) and 100.0% (99.9-100%), respectively. For individuals with deficient or intermediate activity, phenotype sensitivity and specificity was 91.3% (86.4-95.5%) and 92.6% (86.5-96.6%), respectively. For genotype tests evaluating TPMT*2 and TPMT*3, sensitivity and specificity was 88.9% (81.6-97.5%) and 99.2% (98.4-99.9%), respectively. Genotyping has higher sensitivity as long as TPMT*2 and TPMT*3 are tested. Both approaches display high specificity. Latent class meta-analysis is a useful method for synthesizing diagnostic test performance data for clinical practice guidelines.The Pharmacogenomics Journal advance online publication, 24 May 2016; doi:10.1038/tpj.2016.37.
authors.affiliation: Child Health Evaluative Sciences, The Hospital for Sick Children Research Institute, Peter Gilgan Centre for Research and Learning, Toronto, Canada.
authors.forename: R M
authors.initials: RM
authors.lastname: Zur
authors.affiliation: Child Health Evaluative Sciences, The Hospital for Sick Children Research Institute, Peter Gilgan Centre for Research and Learning, Toronto, Canada.
authors.forename: L M
authors.initials: LM
authors.lastname: Roy
authors.affiliation: Division of Clinical Pharmacology and Toxicology, The Hospital for Sick Children, Toronto, Canada.|Departments of Pharmacology & Pharmacy, Faculty of Medicine, Department of Paediatrics, University of Toronto, Toronto, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Ito
authors.affiliation: Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Beyene
authors.affiliation: Centre for Genetic Medicine, The Hospital for Sick Children, Toronto, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Carew
authors.affiliation: Child Health Evaluative Sciences, The Hospital for Sick Children Research Institute, Peter Gilgan Centre for Research and Learning, Toronto, Canada.|Institute for Health Policy, Management & Evaluation, University of Toronto, Toronto, Canada.
authors.forename: W J
authors.initials: WJ
authors.lastname: Ungar
mesh_terms: D019540:Area Under Curve; D004342:Drug Hypersensitivity / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008780:Methyltransferases / Q000235:genetics* / Q000378:metabolism; D000071185:Pharmacogenomic Testing / Q000379:methods*; D000071184:Pharmacogenomic Variants / Q000235:genetics*; D010641:Phenotype; D011237:Predictive Value of Tests; D011686:Purine-Pyrimidine Metabolism, Inborn Errors / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics*; D011687:Purines / Q000009:adverse effects* / Q000378:metabolism; D012372:ROC Curve; D015203:Reproducibility of Results
chemical_list: D011687:Purines; D008780:Methyltransferases; C022745:thiopurine methyltransferase