PMID: 15226673Jul 1, 2004Paper

Comprehensive analysis of thiopurine S-methyltransferase phenotype-genotype correlation in a large population of German-Caucasians and identification of novel TPMT variants

Pharmacogenetics
Elke SchaeffelerMatthias Schwab

Abstract

The thiopurine S-methyltransferase (TPMT) genetic polymorphism has a significant clinical impact on the toxicity of thiopurine drugs. It has been proposed that the identification of patients who are at high risk for developing toxicity on the basis of genotyping could be used to individualize drug treatment. In the present study, phenotype-genotype correlation of 1214 healthy blood donors was investigated to determine the accuracy of genotyping for correct prediction of different TPMT phenotypes. In addition, the influence of gender, age, nicotine and caffeine intake was examined. TPMT red blood cell activity was measured in all samples and genotype was determined for the TPMT alleles *2 and *3. Discordant cases between phenotype and genotype were systematically sequenced. A clearly defined trimodal frequency distribution of TPMT activity was found with 0.6% deficient, 9.9% intermediate and 89.5% normal to high methylators. The frequencies of the mutant alleles were 4.4% (*3A), 0.4% (*3C) and 0.2% (*2). All seven TPMT deficient subjects were homozygous or compound heterozygous carriers for these alleles. In 17 individuals with intermediate TPMT activity discordant to TPMT genotype, four novel variants were identified leading to...Continue Reading

References

May 2, 1978·Clinica Chimica Acta; International Journal of Clinical Chemistry·R M WeinshilboumP A Pazmiño
Apr 1, 1978·Journal of Pharmacokinetics and Biopharmaceutics·K YamaokaT Uno
Apr 7, 1989·Science·G B Elion
Aug 1, 1989·Clinical Pharmacology and Therapeutics·L LennardR M Weinshilboum
Sep 1, 1980·Clinical Pharmacology and Therapeutics·P A PazmiñoR M Weinshilboum
Jan 1, 1995·Genetic Epidemiology·J P VuchetichR A Price
Feb 14, 1995·Proceedings of the National Academy of Sciences of the United States of America·E Y KrynetskiW E Evans
Nov 1, 1993·Scandinavian Journal of Clinical and Laboratory Investigation·B KlemetsdalJ Aarbakke
Jan 1, 1994·Clinical Pharmacology and Therapeutics·H L McLeodW E Evans
Jul 1, 1997·Clinical Pharmacology and Therapeutics·D OtternessR Weinshilboum
Nov 14, 1997·Clinical Pharmacology and Therapeutics·L D LewisD W Nierenberg
Dec 1, 1998·British Journal of Pharmacology·C Spire-Vayron de la MoureyreF Broly
Feb 5, 1999·Human Molecular Genetics·Y Y HonW E Evans
May 20, 1999·Annual Review of Pharmacology and Toxicology·R M WeinshilboumC L Szumlanski
Dec 2, 1999·Journal of the National Cancer Institute·M V RellingW E Evans
Sep 8, 2000·Clinical Pharmacology and Therapeutics·L YanR M Weinshilboum
Apr 17, 2001·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·W E EvansM V Relling
May 25, 2001·European Journal of Clinical Pharmacology·A M RossiG M Pacifici
Apr 23, 2002·Pharmacogenomics·Howard L McLeod, Chokkalingam Siva
Jan 24, 2003·Annual Review of Pharmacology and Toxicology·Allan H Conney
Jun 5, 2003·Pharmacogenetics·Marcelo ReisGuilherme Suarez-Kurtz

❮ Previous
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Citations

May 19, 2012·Inflammatory Bowel Diseases·Frank HoentjenAdriaan A van Bodegraven
Sep 20, 2005·Der Internist·T Gerloff, I Roots
Jun 14, 2005·European Journal of Clinical Pharmacology·Hua-Wen XinUlrich Klotz
Jan 15, 2008·European Journal of Clinical Pharmacology·Shirley Kow Yin KhamAllen Eng Juh Yeoh
May 29, 2008·European Journal of Clinical Pharmacology·Srikumar SahasranamanSandip Roy
Dec 3, 2008·European Journal of Clinical Pharmacology·Edna EfratiEli Sprecher
Feb 10, 2009·European Journal of Clinical Pharmacology·A TemlM Schwab
Jun 4, 2010·European Journal of Clinical Pharmacology·Nancy HakoozWilliam Newman
Jun 29, 2010·European Journal of Clinical Pharmacology·Guillermo GervasiniJuan Antonio Carrillo
Jun 22, 2010·European Journal of Clinical Pharmacology·Ingolf Cascorbi
Mar 27, 2013·Paediatric Drugs·Shahrad Rod RassekhMichael R Hayden
Jul 2, 2005·Nature Genetics·Anna C NeedDavid B Goldstein
Feb 24, 2006·Nature Reviews. Cancer·Meyling H Cheok, William E Evans
Sep 2, 2004·Nature Reviews. Drug Discovery·Richard Weinshilboum, Liewei Wang
Jul 1, 2008·Nature Reviews. Drug Discovery·Scott T WeissKathleen M Giacomini
Jun 30, 2011·Nature Reviews. Nephrology·Pooja Budhiraja, Mordecai Popovtzer
May 26, 2006·European Journal of Human Genetics : EJHG·Tatyana V NasedkinaAlexander S Zasedatelev
Nov 23, 2005·The Pharmacogenomics Journal·B S Shastry
Sep 27, 2006·The Pharmacogenomics Journal·R L RobertsM A Kennedy
Apr 16, 2013·Nucleosides, Nucleotides & Nucleic Acids·Alica ChocholovaBeata Mladosievicova
Jul 5, 2008·Nucleosides, Nucleotides & Nucleic Acids·Ondrej SlanarFrantisek Perlík
Apr 22, 2010·Nucleosides, Nucleotides & Nucleic Acids·Ali BahariBehzad Narouie
Jun 15, 2010·Nucleosides, Nucleotides & Nucleic Acids·S Almer
Aug 22, 2012·Human Molecular Genetics·Chun-Yu WeiYuan-Tsong Chen
Oct 13, 2005·Pharmacogenetics and Genomics·Oreste E SalavaggioneRichard M Weinshilboum
May 3, 2005·Pharmacogenetics and Genomics·Sharon J Gardiner, Evan J Begg
Aug 19, 2008·Pharmacogenetics and Genomics·Shuta UjiieMasahiro Hiratsuka
Sep 30, 2008·Pharmacogenetics and Genomics·Fang LiRichard M Weinshilboum
Feb 16, 2010·Pharmacogenetics and Genomics·Liewei WangTeri E Klein
Mar 5, 2011·Pharmacogenetics and Genomics·Joanna BourgineIngrid Billaut-Laden
Feb 15, 2013·Pharmacogenetics and Genomics·Malin L AppellSally A Coulthard
Aug 13, 2005·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Rashmi R Shah
Jan 18, 2006·Annual Review of Medicine·Michel EichelbaumWilliam E Evans
Jan 13, 2006·Annual Review of Pharmacology and Toxicology·Meyling H CheokWilliam E Evans

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