Explaining TPMT genotype/phenotype discrepancy by haplotyping of TPMT*3A and identification of a novel sequence variant, TPMT*23
2007 (English)In: Pharmacogenetics and Genomics, ISSN 1744-6872, Vol. 17, no 10, 891-895 p.Article in journal (Refereed) Published
Thiopurine methyltransferase (TPMT) is a polymorphic enzyme involved in the metabolism of thiopurine drugs. Owing to polymorphisms in the TPMT gene (TPMT*2-*22), the enzyme activity varies interindividually. Patients with reduced TPMT activity may develop adverse reactions when treated with standard doses of thiopurines. This work focuses on a TPMT genotype/phenotype discrepancy found in a patient during routine testing. The patient displayed very low TPMT enzyme activity and she was genotyped by pyrosequencing as being heterozygous for the 460G>A and 719A>G polymorphisms (TPMT*3A). Complete sequencing in combination with haplotyping of the TPMT gene revealed a novel sequence variant, 500C>G, on one allele and TPMT*3A on the other allele, giving rise to the novel genotype TPMT*3A/*23. When investigating the patient's relatives, they too had the TPMT*3A/*23 genotype in combination with low enzyme activity. We conclude that this novel variant allele affects enzyme activity, as the individuals carrying it had almost undetectable TPMT activity. © 2007 Lippincott Williams & Wilkins, Inc.
Place, publisher, year, edition, pages
2007. Vol. 17, no 10, 891-895 p.
haplotypes, single mucleotide polymorphism, thiopurine methyltransferase
National CategoryMedical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-39374DOI: 10.1097/FPC.0b013e3282ef642bLocal ID: 48065OAI: oai:DiVA.org:liu-39374DiVA: diva2:260223