Document Detail


Ventral midbrain correlation between genetic variation and expression of the dopamine transporter gene in cocaine-abusing versus non-abusing subjects.
MedLine Citation:
PMID:  22026501     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Altered activity of the human dopamine transporter gene (hDAT) is associated with several common and severe brain disorders, including cocaine abuse. However, there is little a priori information on whether such alterations are due to nature (genetic variation) or nurture (human behaviors such as cocaine abuse). This study investigated the correlation between seven markers throughout hDAT and its mRNA levels in postmortem ventral midbrain tissues from 18 cocaine abusers and 18 strictly matched drug-free controls in the African-American population. Here, we show that one major haplotype with the same frequency in cocaine abusers versus drug-free controls displays a 37.1% reduction of expression levels in cocaine abusers compared with matched controls (P=0.0057). The most studied genetic marker, variable number tandem repeats (VNTR) located in Exon 15 (3'VNTR), is not correlated with hDAT mRNA levels. A 5' upstream VNTR (rs70957367) has repeat numbers that are positively correlated with expression levels in controls (r(2)=0.9536, P=0.0235), but this positive correlation disappears in cocaine abusers. The findings suggest that varying hDAT activity is attributable to both genetics and cocaine abuse.
Authors:
Yanhong Zhou; Sharon K Michelhaugh; Carl J Schmidt; Jun S Liu; Michael J Bannon; Zhicheng Lin
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-10-26
Journal Detail:
Title:  Addiction biology     Volume:  19     ISSN:  1369-1600     ISO Abbreviation:  Addict Biol     Publication Date:  2014 Jan 
Date Detail:
Created Date:  2013-12-18     Completed Date:  2014-08-18     Revised Date:  2014-09-13    
Medline Journal Info:
Nlm Unique ID:  9604935     Medline TA:  Addict Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  122-31     Citation Subset:  IM    
Copyright Information:
© 2011 The Authors, Addiction Biology © 2011 Society for the Study of Addiction.
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MeSH Terms
Descriptor/Qualifier:
Adult
African Americans / genetics
Aged
Alleles
Analysis of Variance
Case-Control Studies
Cocaine-Related Disorders / genetics*,  metabolism
Dopamine Plasma Membrane Transport Proteins / drug effects,  genetics*,  metabolism
Epigenesis, Genetic
Exons
Female
Gene Expression / genetics
Gene Expression Regulation / genetics*
Genetic Markers / genetics
Genetic Predisposition to Disease
Genetic Variation / genetics*
Haplotypes
Humans
Linkage Disequilibrium / genetics
Male
Middle Aged
Minisatellite Repeats / genetics
Polymerase Chain Reaction / methods
Polymorphism, Restriction Fragment Length / genetics
RNA, Messenger / metabolism*
Ventral Tegmental Area / metabolism*
Grant Support
ID/Acronym/Agency:
R01 DA006470/DA/NIDA NIH HHS; R01 DA021409/DA/NIDA NIH HHS; R01 DA021409-05/DA/NIDA NIH HHS; R01DA006470/DA/NIDA NIH HHS; R01DA021409/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/Dopamine Plasma Membrane Transport Proteins; 0/Genetic Markers; 0/RNA, Messenger

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


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