ParkinsonCanadaV1, Main, Exploration, bibRecord, 000680

Increased Nigral SLC6A3 Activity in Schizophrenia Patients: Findings From the Toronto–McLean Cohorts

Identifieur interne : 000680 ( Main/Exploration ); précédent : 000679; suivant : 000681

Increased Nigral SLC6A3 Activity in Schizophrenia Patients: Findings From the Toronto–McLean Cohorts

Auteurs : James L. Kennedy [Canada] ; Nian Xiong [République populaire de Chine] ; Jinlong Yu ; Clement C. Zai [Canada] ; Jennie G. Pouget [Canada] ; Jie Li [République populaire de Chine] ; Kefu Liu [République populaire de Chine] ; Hong Qing [République populaire de Chine] ; Tao Wang [République populaire de Chine] ; Eden Martin ; Deborah L. Levy [États-Unis] ; Zhicheng Lin

Source :

Schizophrenia Bulletin [ 0586-7614 ] ; 2015.

RBID : PMC:4838105

Abstract

SLC6A3, which encodes the primary regulator of extracellular dopamine (DA) concentration, the DA transporter, has been implicated in schizophrenia (SCZ). However, the details of its genetic effect on risk remain largely unknown. The purpose of this candidate gene study was to identify a specific SLC6A3 activity associated with SCZ by using functional genetic approaches. We first examined gene activity in DA neurons isolated from case-control postmortem nigral tissue and found that the average SLC6A3 mRNA level in controls was only 0.37-fold of that in cases (P = .0034). To understand this expression difference, we examined the association of 10 genetic markers, mostly located in the promoter region, with SCZ in 1717 subjects collected from Toronto and McLean cohorts, including 881 controls and 836 cases and identified the 5′ promoter SNP rs1478435 as having a significant association signal (uncorrected P value: .00462; adjusted P value: .0319) in unrelated Caucasians. Allele T was over-represented in controls (OR = .75); T-carrier controls had decreased mRNA levels in nigral DA neurons, contributing to the reduced activity in the controls. In vitro functional analysis confirmed that T carriers displayed attenuated enhancement of promoter activity. These findings collectively suggest that increased nigral SLC6A3 activity may be a risk factor for SCZ, and may help to explain high rates of comorbidity with substance abuse.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4838105

DOI: 10.1093/schbul/sbv191
PubMed: 26707863
PubMed Central: 4838105

Affiliations:

Le document en format XML

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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Increased Nigral <italic>SLC6A3</italic>
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<author><name sortKey="Lin, Zhicheng" sort="Lin, Zhicheng" uniqKey="Lin Z" first="Zhicheng" last="Lin">Zhicheng Lin</name>
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<series><title level="j">Schizophrenia Bulletin</title>
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<front><div type="abstract" xml:lang="en"><p><italic>SLC6A3</italic>
, which encodes the primary regulator of extracellular dopamine (DA) concentration, the DA transporter, has been implicated in schizophrenia (SCZ). However, the details of its genetic effect on risk remain largely unknown. The purpose of this candidate gene study was to identify a specific <italic>SLC6A3</italic>
 activity associated with SCZ by using functional genetic approaches. We first examined gene activity in DA neurons isolated from case-control postmortem nigral tissue and found that the average <italic>SLC6A3</italic>
 mRNA level in controls was only 0.37-fold of that in cases (<italic>P</italic>
 = .0034). To understand this expression difference, we examined the association of 10 genetic markers, mostly located in the promoter region, with SCZ in 1717 subjects collected from Toronto and McLean cohorts, including 881 controls and 836 cases and identified the 5′ promoter SNP rs1478435 as having a significant association signal (uncorrected <italic>P</italic>
 value: .00462; adjusted <italic>P</italic>
 value: .0319) in unrelated Caucasians. Allele T was over-represented in controls (OR = .75); T-carrier controls had decreased mRNA levels in nigral DA neurons, contributing to the reduced activity in the controls. In vitro functional analysis confirmed that T carriers displayed attenuated enhancement of promoter activity. These findings collectively suggest that increased nigral <italic>SLC6A3</italic>
 activity may be a risk factor for SCZ, and may help to explain high rates of comorbidity with substance abuse.</p>
</div>
</front>
</TEI>
<affiliations><list><country><li>Canada</li>
<li>République populaire de Chine</li>
<li>États-Unis</li>
</country>
<region><li>Massachusetts</li>
</region>
</list>
<tree><noCountry><name sortKey="Lin, Zhicheng" sort="Lin, Zhicheng" uniqKey="Lin Z" first="Zhicheng" last="Lin">Zhicheng Lin</name>
<name sortKey="Martin, Eden" sort="Martin, Eden" uniqKey="Martin E" first="Eden" last="Martin">Eden Martin</name>
<name sortKey="Yu, Jinlong" sort="Yu, Jinlong" uniqKey="Yu J" first="Jinlong" last="Yu">Jinlong Yu</name>
</noCountry>
<country name="Canada"><noRegion><name sortKey="Kennedy, James L" sort="Kennedy, James L" uniqKey="Kennedy J" first="James L." last="Kennedy">James L. Kennedy</name>
</noRegion>
<name sortKey="Kennedy, James L" sort="Kennedy, James L" uniqKey="Kennedy J" first="James L." last="Kennedy">James L. Kennedy</name>
<name sortKey="Kennedy, James L" sort="Kennedy, James L" uniqKey="Kennedy J" first="James L." last="Kennedy">James L. Kennedy</name>
<name sortKey="Pouget, Jennie G" sort="Pouget, Jennie G" uniqKey="Pouget J" first="Jennie G." last="Pouget">Jennie G. Pouget</name>
<name sortKey="Pouget, Jennie G" sort="Pouget, Jennie G" uniqKey="Pouget J" first="Jennie G." last="Pouget">Jennie G. Pouget</name>
<name sortKey="Pouget, Jennie G" sort="Pouget, Jennie G" uniqKey="Pouget J" first="Jennie G." last="Pouget">Jennie G. Pouget</name>
<name sortKey="Zai, Clement C" sort="Zai, Clement C" uniqKey="Zai C" first="Clement C." last="Zai">Clement C. Zai</name>
<name sortKey="Zai, Clement C" sort="Zai, Clement C" uniqKey="Zai C" first="Clement C." last="Zai">Clement C. Zai</name>
<name sortKey="Zai, Clement C" sort="Zai, Clement C" uniqKey="Zai C" first="Clement C." last="Zai">Clement C. Zai</name>
</country>
<country name="République populaire de Chine"><noRegion><name sortKey="Xiong, Nian" sort="Xiong, Nian" uniqKey="Xiong N" first="Nian" last="Xiong">Nian Xiong</name>
</noRegion>
<name sortKey="Li, Jie" sort="Li, Jie" uniqKey="Li J" first="Jie" last="Li">Jie Li</name>
<name sortKey="Liu, Kefu" sort="Liu, Kefu" uniqKey="Liu K" first="Kefu" last="Liu">Kefu Liu</name>
<name sortKey="Qing, Hong" sort="Qing, Hong" uniqKey="Qing H" first="Hong" last="Qing">Hong Qing</name>
<name sortKey="Wang, Tao" sort="Wang, Tao" uniqKey="Wang T" first="Tao" last="Wang">Tao Wang</name>
</country>
<country name="États-Unis"><region name="Massachusetts"><name sortKey="Levy, Deborah L" sort="Levy, Deborah L" uniqKey="Levy D" first="Deborah L." last="Levy">Deborah L. Levy</name>
</region>
</country>
</tree>
</affiliations>
</record>

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La maladie de Parkinson au Canada (serveur d'exploration)

Increased Nigral SLC6A3 Activity in Schizophrenia Patients: Findings From the Toronto–McLean Cohorts

Increased Nigral SLC6A3 Activity in Schizophrenia Patients: Findings From the Toronto–McLean Cohorts

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	La maladie de Parkinson au Canada (serveur d'exploration)
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