Ventral midbrain correlation between genetic variation and expression of the dopamine transporter gene in cocaine-abusing versus non-abusing subjects

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Ventral midbrain correlation between genetic variation and expression of the dopamine transporter gene in cocaine-abusing versus non-abusing subjects

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Title: Ventral midbrain correlation between genetic variation and expression of the dopamine transporter gene in cocaine-abusing versus non-abusing subjects
Author: Zhou, Yanhong; Michelhaugh, Sharon K.; Schmidt, Carl J.; Liu, Jun; Bannon, Michael J.; Lin, Zhicheng

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Citation: Zhou, Yanhong, Sharon K. Michelhaugh, Carl J. Schmidt, Jun S. Liu, Michael J. Bannon, and Zhicheng Lin. 2011. “Ventral Midbrain Correlation Between Genetic Variation and Expression of the Dopamine Transporter Gene in Cocaine-Abusing Versus Non-Abusing Subjects.” Addiction Biology 19 (1) (October 26): 122–131. doi:10.1111/j.1369-1600.2011.00391.x. http://dx.doi.org/10.1111/j.1369-1600.2011.00391.x.
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Abstract: Altered activity of the human dopamine transporter gene (hDAT) is asssociated with several common and severe brain disorders including cocaine abuse. However, there is little a priori information on whether such alteration was due to nature (genetic variantion) 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 same frequency in cocaine abusers versus drug-free controls displays a 37.1%-reduction of expression levels in cocaine abusers, compared to 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 positively correlated with expression levels in controls (r2 0.9536, P = 0.0235) but this positive correlation disappears in cocaine abusers. The findings suggest that varying hDAT activity is attributed to both genetics and cocaine abuse.
Published Version: doi:10.1111/j.1369-1600.2011.00391.x
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3270208/
Terms of Use: This article is made available under the terms and conditions applicable to Open Access Policy Articles, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#OAP
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:27002571
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