Genotype and ancestry modulate brain's DAT availability in healthy humans
Abstract
The dopamine transporter (DAT) is a principal regulator of dopaminergic neurotransmission and its gene (the SLC6A3) is a strong biological candidate gene for various behavioral- and neurological disorders. Intense investigation of the link between the SLC6A3 polymorphisms and behavioral phenotypes yielded inconsistent and even contradictory results. Reliance on objective brain phenotype measures, for example, those afforded by brain imaging, might critically improve detection of DAT genotype-phenotype association. Here, we tested the relationship between the DAT brain availability and the SLC6A3 genotypes using an aggregate sample of 95 healthy participants of several imaging studies. These studies employed positron emission tomography (PET) with [{sup 11}C] cocaine wherein the DAT availability was estimated as Bmax/Kd; while the genotype values were obtained on two repeat polymorphisms - 3-UTR- and intron 8- VNTRs. The main findings are the following: (1) both polymorphisms analyzed as single genetic markers and in combination (haplotype) modulate DAT density in midbrain; (2) ethnic background and age influence the strength of these associations; and (3) age-related changes in DAT availability differ in the 3-UTR and intron8 - genotype groups.
- Authors:
- Publication Date:
- Research Org.:
- Brookhaven National Lab. (BNL), Upton, NY (United States)
- Sponsoring Org.:
- USDOE SC OFFICE OF SCIENCE (SC)
- OSTI Identifier:
- 1040508
- Report Number(s):
- BNL-96299-2011-JA
Journal ID: ISSN 1932-6203; R&D Project: MO-085; TRN: US1202476
- DOE Contract Number:
- DE-AC02-98CH10886
- Resource Type:
- Journal Article
- Journal Name:
- PLoS ONE
- Additional Journal Information:
- Journal Volume: 6; Journal Issue: 8; Journal ID: ISSN 1932-6203
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 62 RADIOLOGY AND NUCLEAR MEDICINE; 38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY; AVAILABILITY; BRAIN; COCAINE; DETECTION; DOPAMINE; GENES; GENETICS; GENOTYPE; INTRONS; PHENOTYPE; POSITRON COMPUTED TOMOGRAPHY; dopamine transporter (DAT); phenotypes; cocaine
Citation Formats
Shumay, E, Shumay, E, Chen, J, Fowler, J S, and Volkow, N D. Genotype and ancestry modulate brain's DAT availability in healthy humans. United States: N. p., 2011.
Web. doi:10.1371/journal.pone.0022754.
Shumay, E, Shumay, E, Chen, J, Fowler, J S, & Volkow, N D. Genotype and ancestry modulate brain's DAT availability in healthy humans. United States. https://doi.org/10.1371/journal.pone.0022754
Shumay, E, Shumay, E, Chen, J, Fowler, J S, and Volkow, N D. 2011.
"Genotype and ancestry modulate brain's DAT availability in healthy humans". United States. https://doi.org/10.1371/journal.pone.0022754.
@article{osti_1040508,
title = {Genotype and ancestry modulate brain's DAT availability in healthy humans},
author = {Shumay, E and Shumay, E and Chen, J and Fowler, J S and Volkow, N D},
abstractNote = {The dopamine transporter (DAT) is a principal regulator of dopaminergic neurotransmission and its gene (the SLC6A3) is a strong biological candidate gene for various behavioral- and neurological disorders. Intense investigation of the link between the SLC6A3 polymorphisms and behavioral phenotypes yielded inconsistent and even contradictory results. Reliance on objective brain phenotype measures, for example, those afforded by brain imaging, might critically improve detection of DAT genotype-phenotype association. Here, we tested the relationship between the DAT brain availability and the SLC6A3 genotypes using an aggregate sample of 95 healthy participants of several imaging studies. These studies employed positron emission tomography (PET) with [{sup 11}C] cocaine wherein the DAT availability was estimated as Bmax/Kd; while the genotype values were obtained on two repeat polymorphisms - 3-UTR- and intron 8- VNTRs. The main findings are the following: (1) both polymorphisms analyzed as single genetic markers and in combination (haplotype) modulate DAT density in midbrain; (2) ethnic background and age influence the strength of these associations; and (3) age-related changes in DAT availability differ in the 3-UTR and intron8 - genotype groups.},
doi = {10.1371/journal.pone.0022754},
url = {https://www.osti.gov/biblio/1040508},
journal = {PLoS ONE},
issn = {1932-6203},
number = 8,
volume = 6,
place = {United States},
year = {Mon Aug 01 00:00:00 EDT 2011},
month = {Mon Aug 01 00:00:00 EDT 2011}
}