ArticleEuropean journal of clinical pharmacology2009
Distribution of TPMT risk alleles for thiopurine [correction of thioupurine] toxicity in the Israeli population.
Article in European journal of clinical pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 25 citations in OpenAlex.
- Thiopurine S-Methyltransferase as a Pharmacogenetic Biomarker: Significance of Testing and Review of Major Methods.Cardiovascular & hematological agents in medicinal chemistry · 2017Review
- Thiopurine S-methyltransferase (TPMT) activity is better determined by biochemical assay versus genotyping in the Jewish population.Digestive diseases and sciences · 2014Article
- Thiopurine methyltransferase genotyping in Palestinian childhood acute lymphoblastic leukemia patients.BMC hematology · 2013Article
- Frequency of thiopurine S-methyltransferase mutant alleles in indigenous and admixed Guatemalan patients with acute lymphoblastic leukemia.Medical oncology (Northwood, London, England) · 2013Article
- Genetic analysis of thiopurine methyltransferase polymorphism in the Jordanian population.European journal of clinical pharmacology · 2010Article
- Pretreatment determination of TPMT--state of the art in clinical practice.European journal of clinical pharmacology · 2009Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectiveIndividuals with intermediate or no thiopurine S-methyltransferase (TPMT) activity are at risk of hematotoxicity when treated with standard doses of thiopurines, thus, pretreatment identification of these individuals is of major importance. The purpose of this study was to determine the frequency and distribution of TPMT polymorphic variants, known to functionally impair TPMT activity, in the highly heterogeneous Israeli population.
methodsTPMT genotyping of individuals representing three major demographic groups in Israel was carried out by PCR restriction fragment length polymorphism and high-resolution melting.
resultsFrequencies of TPMT risk alleles differed significantly among the screened Israeli subpopulations: Druze showed fivefold and twofold higher frequencies than Jews and Moslems, respectively. Specifically, allelic frequencies of TPMT*3A were 0.73% (95% CI 0.34-1.45%), 0.79% (95% CI 0.16-2.39%), and 3.19% (95% CI 1.78-5.58%) in Jews, Moslems, and Druze, respectively. Although not found in Jews, TPMT*3C was found at an allelic frequency of 1.05% (95% CI 0.31-2.76%) and 0.75% (95% CI 0.02-2.84%) in Moslems and Druze. TPMT*2 and TPMT*3B were not detected in any of the Israeli subpopulations studied.
conclusionThese data indicate that the Israeli population displays a distinct TPMT genetic variability that is comprised of a mix of three major genetically diverse subpopulations, each with its unique TPMT allelic frequency distribution pattern and likelihood of developing an adverse reaction to thiopurine drugs.
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