Thiopurine methyltransferase pharmacogenetics: alternative molecular diagnosis and preliminary data from Northern Portugal

• Type: Article in International Scientific Journal
• Date: 1999

Authors

Alves, S (Author) Other; Prata, MJ (Author) FCUP; Ferreira, F (Author) Other; Amorim, A (Author) FCUP

Journal

Title: Pharmacogenetics

Vol. 9

Pages: 257-261

ISSN: 0960-314X

Publisher: Lippincott Williams & Wilkins Ltd.

Indexing

ISI Web of Knowledge - 25 Citations

Scopus - 29 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-001-4S9

Abstract (EN): The thiopurine methyltransferase (TPMT) genetic polymorphism has been shown to have a highly significant clinical impact, namely in the therapeutic efficiency of thiopurine drugs used in the treatment of a wide range of diseases. Available diagnostic methods, although reproducible and sensitive, are relatively laborious. Thus population studies are still very scarce. In this work we describe a new polymerase chain reaction-single strand confirmational analysis based protocol for TPMT specific detection which introduces a substantial technical simplification avoiding the use of restriction enzyme treatment after polymerase chain reaction amplification, Additionally, the use of this protocol allows the simultaneous detection of a T-474 to C substitution, a frequent silent mutation in the North Portuguese population (TPMT*1S = 0.215). In a sample of 310 unrelated Northern Portuguese individuals, 15 were found to be heterozygous for the TPMT*3A allele (defined by the presence of two transitions, G(460) to A and A(719) to G) which is associated with TPMT enzymatic deficiency; the corresponding gene frequency estimate was 0.024. We also attempted to evaluate the relationship between the molecular TPMT genotype and the reaction to treatments involving thiopurine drugs by analysing a sample of 24 children submitted to curative therapy of acute lymphoblastic leukaemia. Four of them were shown to be heterozygous for the TPMT*3A allele. An examination of their clinical histories showed that all four patients exhibited signs of severe hepatic toxicity during treatment. Pharmacogenetics 9:257-261 (C) 1999 Lippincott Williams & Wilkins.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 5