Explaining TPMT genotype/phenotype discrepancy by identification of a novel sequence variant, TPMT*27
2009 (English)In: 13th International Symposium on Purine and Pyrimidine metabolism in man, 2009Conference paper (Refereed)
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.
Place, publisher, year, edition, pages
National CategoryMedical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-21181OAI: oai:DiVA.org:liu-21181DiVA: diva2:240856