Ventral midbrain correlation between genetic variation and expression of the dopamine transporter gene in cocaine-abusing versus non-abusing subjects.
Addict Biol
; 19(1): 122-31, 2014 Jan.
Article
em En
| MEDLINE
| ID: mdl-22026501
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Variação Genética
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RNA Mensageiro
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Regulação da Expressão Gênica
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Área Tegmentar Ventral
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Transtornos Relacionados ao Uso de Cocaína
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Proteínas da Membrana Plasmática de Transporte de Dopamina
Tipo de estudo:
Observational_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Addict Biol
Assunto da revista:
TRANSTORNOS RELACIONADOS COM SUBSTANCIAS
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos