Linked Life Data

10022246

Source:http://linkedlifedata.com/resource/pubmed/id/10022246

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1999-2-25
pubmed:abstractText
The cytochrome P450 superfamily is known to exhibit a high degree of genetic polymorphism and polymorphisms associated with absent or low enzyme activity in CYP2D6, CYP2C19 and CYP2C9 are particularly well studied. However, despite early reports of strong disease associations for particular CYP2D6 phenotypes, these have not been confirmed in recent, more detailed studies and it now appears that analysis of CYP2D6, CYP2C19 and CYP2C9 genotype is of most value in predicting metabolism of specific drugs. Polymorphisms in other cytochrome P450 genes are less well studied and appear not to be associated with complete absence of enzyme activity. We have recently carried out studies of polymorphism in both CYP1A1 and CYP2E1. The molecular basis of the apparent CYP1A1 'high inducibility' polymorphism was investigated by studying CYP1A1 and Ah receptor polymorphisms in a group of phenotyped individuals who were genotyped both for known and novel CYP1A1 and Ah receptor polymorphisms. Three novel polymorphisms in CYP1A1 (C(-459)T, G(-469)A and C(4151)T) and one in the Ah receptor (G(1768)A; V(570)I) were detected by single strand conformational polymorphism analysis and DNA sequencing. Among both novel and previously known polymorphisms, only the Ah receptor G(1721)A polymorphism, which has an allele frequency of 0.12 in Caucasians and was detected previously in a Japanese population, was significantly associated with high induced CYP1A1 activity. In the case of CYP2E1, we have detected three polymorphisms in the promoter region (A(-316)G, T(-297)A and G(-35)T) and one in the coding sequence (G(4804)A; V(179)I) by screening Caucasian DNA samples. The significance of these alleles has been investigated but only G(-35)T combined with T(-297)A, which has an allele frequency of 0.05, appears to be of functional significance, with an apparent 1.8-fold increase in levels of transcriptional activity compared with the wild-type.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0378-4274
pubmed:author
pubmed:issnType
Print
pubmed:day
28
pubmed:volume
102-103
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
143-7
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Recent advances in understanding the molecular basis of polymorphisms in genes encoding cytochrome P450 enzymes.
pubmed:affiliation
Department of Pharmacological Sciences, Medical School, University of Newcastle upon Tyne, UK. a.k.daly@newcastle.ac.uk
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't