Linked Life Data

10376773

Source:http://linkedlifedata.com/resource/pubmed/id/10376773

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1999-7-16
pubmed:abstractText
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 T474 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, G460 to A and A719 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0960-314X
pubmed:author
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
257-61
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Thiopurine methyltransferase pharmacogenetics: alternative molecular diagnosis and preliminary data from Northern Portugal.
pubmed:affiliation
IPATIMUP, Faculdade de Ciências da Universidade do Porto, Portugal.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't