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

• Tipo: Artigo em Revista Científica Internacional
• Data: 1999

Autores

Alves, S (Autor) Outra; Prata, MJ (Autor) FCUP; Ferreira, F (Autor) Outra; Amorim, A (Autor) FCUP

Revista

Título: Pharmacogenetics

Vol. 9

Páginas: 257-261

ISSN: 0960-314X

Editora: Lippincott Williams & Wilkins Ltd.

Indexação

ISI Web of Knowledge - 25 Citações

Scopus - 29 Citações

Classificação Científica

FOS: Ciências médicas e da saúde > Medicina básica

Outras Informações

ID Authenticus: 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 5