Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2006-4-19
pubmed:abstractText
Animal models suggest that the casein kinase 1 epsilon gene (Csnk1e) contributes to variability in stimulant response. Csnk1e is a key component in the Darpp-32 (Dopamine-And-cAMP-Regulated-Phosphoprotein-32 kDa) second messenger pathway and has been implicated in previous pharmacological and pharmacogenetic studies in mice. Mice bred for methamphetamine sensitivity showed linkage to the region of chromosome 15 that contains Csnk1e and also showed a 10-fold increase in expression of Csnk1e. We used a double-blind, crossover design in healthy human volunteers to test association between polymorphisms in the CSNK1E region and subjective response to placebo, 10, or 20 mg of oral D-amphetamine. Repeated-measures ANOVA was used to analyze interactions between genotype and drug response. The primary outcome measure, subjects' ratings of whether they felt a drug effect (Drug Effects Questionnaire (DEQ)), revealed a significant effect (p=0.010) at one single-nucleotide polymorphism (rs135745). Subjects with more copies of the rs135745 C allele were more sensitive to the low dose of D-amphetamine (p=0.001), which corresponded to a leftward shift in the dose-response curve. These findings demonstrate the successful translation of pharmacogenetic results from mice to humans.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0893-133X
pubmed:author
pubmed:issnType
Print
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1056-63
pubmed:dateRevised
2011-5-18
pubmed:meshHeading
pubmed-meshheading:16237383-Adolescent, pubmed-meshheading:16237383-Adult, pubmed-meshheading:16237383-Animals, pubmed-meshheading:16237383-Brain, pubmed-meshheading:16237383-Brain Chemistry, pubmed-meshheading:16237383-Casein Kinase Iepsilon, pubmed-meshheading:16237383-Central Nervous System Stimulants, pubmed-meshheading:16237383-Cross-Over Studies, pubmed-meshheading:16237383-Dextroamphetamine, pubmed-meshheading:16237383-Dopamine and cAMP-Regulated Phosphoprotein 32, pubmed-meshheading:16237383-Dose-Response Relationship, Drug, pubmed-meshheading:16237383-Double-Blind Method, pubmed-meshheading:16237383-Drug Tolerance, pubmed-meshheading:16237383-Female, pubmed-meshheading:16237383-Gene Frequency, pubmed-meshheading:16237383-Humans, pubmed-meshheading:16237383-Male, pubmed-meshheading:16237383-Mice, pubmed-meshheading:16237383-Models, Animal, pubmed-meshheading:16237383-Polymorphism, Genetic, pubmed-meshheading:16237383-Polymorphism, Single Nucleotide, pubmed-meshheading:16237383-Questionnaires
pubmed:year
2006
pubmed:articleTitle
Association between the casein kinase 1 epsilon gene region and subjective response to D-amphetamine.
pubmed:affiliation
Institute of Juvenile Research, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 60637, USA.
pubmed:publicationType
Journal Article, Comparative Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural