Document Detail


Association of dopamine, serotonin, and nicotinic gene polymorphisms with methylphenidate response in ADHD.
MedLine Citation:
PMID:  17948872     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Gene polymorphisms of the 3' untranslated region (3'-UTR) of the dopamine transporter (DAT1), Dopamine receptor exon 3 D4 variable number tandem repeat (DRD4VNTR), nicotinic acetylcholine receptor alpha 4 subunit (CHRNA4) and serotonin transporter promoter (SLC6A4-5HTTLPR) are under consideration as potential risk factors for attention-deficit/hyperactivity disorder (ADHD). A post-hoc attempt was made to investigate the association between the allelic variations of these candidate genes and retrospective parental report of response to methylphenidate in an ADHD-enriched, population-based twin sample. Subjects (N = 243) were selected from the twin sample based on parent report that the child had been treated with methylphenidate for ADHD symptoms. The functional polymorphisms screened were the VNTR located in the 3'-UTR of the dopamine transporter, DRD4 VNTR, CHRNA4 (rs1044396 and rs6090384) and the long (L(A) and L(G)) and short (S) forms of the serotonin transporter promoter region. Logistic regression did not demonstrate a significant association between methylphenidate treatment response and the relevant polymorphisms. The sample size had high power to detect effect sizes similar to those reported in some prior methylphenidate pharmacogenetic studies; however, the categorical (yes/no) measure of parent-reported treatment response may not have been sensitive enough to pick up statistically significant differences in treatment response based on genotype. Further studies including quantitative measures of treatment response are warranted.
Authors:
Hema Tharoor; Elizabeth A Lobos; Richard D Todd; Angela M Reiersen
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Twin Study    
Journal Detail:
Title:  American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics     Volume:  147B     ISSN:  1552-485X     ISO Abbreviation:  Am. J. Med. Genet. B Neuropsychiatr. Genet.     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-05-26     Completed Date:  2008-07-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101235742     Medline TA:  Am J Med Genet B Neuropsychiatr Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  527-30     Citation Subset:  IM    
Copyright Information:
(c) 2007 Wiley-Liss, Inc.
Affiliation:
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA. hematharoor@hotmail.com
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Attention Deficit Disorder with Hyperactivity / drug therapy*,  genetics*
Child
DNA Mutational Analysis
Dopamine Plasma Membrane Transport Proteins / genetics*
Female
Humans
Male
Methylphenidate / pharmacokinetics*
Minisatellite Repeats
Pharmacogenetics
Polymorphism, Genetic*
Polymorphism, Single Nucleotide
Receptors, Dopamine D4 / genetics*
Receptors, Nicotinic / genetics*
Retrospective Studies
Serotonin Plasma Membrane Transport Proteins / genetics*
Grant Support
ID/Acronym/Agency:
05811//PHS HHS; 17104//PHS HHS; 52813//PHS HHS
Chemical
Reg. No./Substance:
0/DRD4 protein, human; 0/Dopamine Plasma Membrane Transport Proteins; 0/Receptors, Nicotinic; 0/SLC6A3 protein, human; 0/SLC6A4 protein, human; 0/Serotonin Plasma Membrane Transport Proteins; 0/nicotinic acetylcholine receptor alpha4 subunit; 113-45-1/Methylphenidate; 137750-34-6/Receptors, Dopamine D4

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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