Ventral midbrain correlation between genetic variation and expression of the dopamine transporter gene in cocaine-abusing versus non-abusing subjects.
Ventral midbrain correlation between genetic variation and expression of the dopamine transporter gene in cocaine-abusing versus non-abusing subjects.
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可卡因滥用者与非滥用者的遗传变异与多巴胺转运蛋白基因表达之间的腹中脑相关性。
DOI：
10.1111/j.1369-1600.2011.00391.x
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发表时间：
2014
影响因子：
3.4
通讯作者：
Lin,Zhicheng
中科院分区：
文献类型：
--
作者：
Zhou,Yanhong;Michelhaugh,SharonK;Schmidt,CarlJ;Liu,JunS;Bannon,MichaelJ;Lin,Zhicheng
人类多巴胺转运蛋白基因 (hDAT) 活性的改变与几种常见和严重的脑部疾病有关，包括可卡因滥用。然而，关于这种改变是由于自然（遗传变异）还是后天（诸如可卡因滥用等人类行为）造成的先验信息很少。本研究调查了非洲裔美国人群体中 18 名可卡因滥用者和 18 名严格匹配的无毒品对照者死后腹侧中脑组织中 hDAT 的 7 个标记与其 mRNA 水平之间的相关性。在这里，我们发现可卡因滥用者与无毒品对照者中频率相同的一种主要单倍型显示，与匹配对照者相比，可卡因滥用者的表达水平降低了 37.1%（P= 0.0057）。研究最多的遗传标记，位于外显子 15 (3'VNTR) 的可变数目串联重复序列 (VNTR)，与 hDATmRNA 水平不相关。 5'上游VNTR（rs70957367）的重复次数与对照中的表达水平呈正相关（r2= 0.9536，P= 0.0235），但这种正相关在可卡因滥用者中消失。研究结果表明，不同的 hDAT 活性可归因于遗传和可卡因滥用。
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 throughouthDATand 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 withhDATmRNA levels. A 5′ upstream VNTR (rs70957367) has repeat numbers that are 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 varyinghDATactivity is attributable to both genetics and cocaine abuse.