Linked Life Data

18214865

Source:http://linkedlifedata.com/resource/pubmed/id/18214865

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2008-11-25
pubmed:abstractText
Methylphenidate is the most frequently prescribed drug in the treatment of attention deficit hyperactivity disorder (ADHD) but it is not effective in every case. Therefore, identifying genetic and/or biological markers predicting drug-response is increasingly important. Here we present a case-control study and pharmacogenetic association analyses in ADHD investigating three dopaminergic polymorphisms. Previous studies suggested variable number of tandem repeats (VNTR) in the dopamine D4 receptor (DRD4) and the dopamine transporter (DAT1) genes as genetic risk factors for ADHD and as possible markers of methylphenidate response. Our results did not indicate substantial involvement of these two VNTRs in ADHD, however, both the case-control and the pharmacogenetic analyses showed significant role of the high activity Val-allele of cathecol-O-methyltransferase (COMT) Val158Met polymorphism in our ADHD population. The Val-allele was more frequent in the ADHD group (n = 173) compared to the healthy population (P = 0.016). The categorical analysis of 90 responders versus 32 non-responders showed an association between the Val-allele or Val/Val genotype and good methylphenidate response (P = 0.009 and P = 0.034, respectively). Analyzing symptom severity as a continuous trait, significant interaction of COMT genotype and methylphenidate was found on the Hyperactivity-Impulsivity scale (P = 0.044). Symptom severity scores of all three genotype groups decreased following methylphenidate administration (P < 0.001), however Val/Val homozygote children had significantly less severe symptoms than those with Met/Met genotype after treatment (P = 0.015). This interaction might reflect the regulatory effect of COMT dominated prefrontal dopamine transmission on subcortical dopamine systems, which are the actual site of methylphenidate action.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1552-485X
pubmed:author
pubmed:copyrightInfo
Copyright 2008 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:day
5
pubmed:volume
147B
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1431-5
pubmed:meshHeading
pubmed-meshheading:18214865-Alleles, pubmed-meshheading:18214865-Attention Deficit Disorder with Hyperactivity, pubmed-meshheading:18214865-Case-Control Studies, pubmed-meshheading:18214865-Catechol O-Methyltransferase, pubmed-meshheading:18214865-Central Nervous System Stimulants, pubmed-meshheading:18214865-Chi-Square Distribution, pubmed-meshheading:18214865-Child, pubmed-meshheading:18214865-Dopamine Plasma Membrane Transport Proteins, pubmed-meshheading:18214865-Dose-Response Relationship, Drug, pubmed-meshheading:18214865-Female, pubmed-meshheading:18214865-Gene Frequency, pubmed-meshheading:18214865-Humans, pubmed-meshheading:18214865-Male, pubmed-meshheading:18214865-Methylphenidate, pubmed-meshheading:18214865-Minisatellite Repeats, pubmed-meshheading:18214865-Pharmacogenetics, pubmed-meshheading:18214865-Polymorphism, Genetic, pubmed-meshheading:18214865-Prospective Studies, pubmed-meshheading:18214865-Receptors, Dopamine D4, pubmed-meshheading:18214865-Severity of Illness Index, pubmed-meshheading:18214865-Treatment Outcome
pubmed:year
2008
pubmed:articleTitle
Catechol-O-methyltransferase Val158Met polymorphism is associated with methylphenidate response in ADHD children.
pubmed:affiliation
Institute of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't