Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2001-11-5
pubmed:abstractText
Geographic patterns of genetic variation, including variation at drug metabolizing enzyme (DME) loci and drug targets, indicate that geographic structuring of inter-individual variation in drug response may occur frequently. This raises two questions: how to represent human population genetic structure in the evaluation of drug safety and efficacy, and how to relate this structure to drug response. We address these by (i) inferring the genetic structure present in a heterogeneous sample and (ii) comparing the distribution of DME variants across the inferred genetic clusters of individuals. We find that commonly used ethnic labels are both insufficient and inaccurate representations of the inferred genetic clusters, and that drug-metabolizing profiles, defined by the distribution of DME variants, differ significantly among the clusters. We note, however, that the complexity of human demographic history means that there is no obvious natural clustering scheme, nor an obvious appropriate degree of resolution. Our comparison of drug-metabolizing profiles across the inferred clusters establishes a framework for assessing the appropriate level of resolution in relating genetic structure to drug response.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1061-4036
pubmed:author
pubmed:issnType
Print
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
265-9
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11685208-Chi-Square Distribution, pubmed-meshheading:11685208-Chromosomes, Human, Pair 1, pubmed-meshheading:11685208-Cluster Analysis, pubmed-meshheading:11685208-Continental Population Groups, pubmed-meshheading:11685208-Cytochrome P-450 Enzyme System, pubmed-meshheading:11685208-Enzymes, pubmed-meshheading:11685208-Ethnic Groups, pubmed-meshheading:11685208-Gene Frequency, pubmed-meshheading:11685208-Genetic Variation, pubmed-meshheading:11685208-Genotype, pubmed-meshheading:11685208-Humans, pubmed-meshheading:11685208-Male, pubmed-meshheading:11685208-Microsatellite Repeats, pubmed-meshheading:11685208-Multifactorial Inheritance, pubmed-meshheading:11685208-Oxidation-Reduction, pubmed-meshheading:11685208-Pharmaceutical Preparations, pubmed-meshheading:11685208-Pharmacogenetics, pubmed-meshheading:11685208-Polymorphism, Single Nucleotide, pubmed-meshheading:11685208-Software, pubmed-meshheading:11685208-X Chromosome
pubmed:year
2001
pubmed:articleTitle
Population genetic structure of variable drug response.
pubmed:affiliation
Galton Laboratory, Department of Biology, University College London, London, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't