Genotype and ancestry modulate brain's DAT availability in healthy humans
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.
- Research Organization:
- BROOKHAVEN NATIONAL LABORATORY (BNL)
- Sponsoring Organization:
- USDOE SC OFFICE OF SCIENCE (SC)
- DOE Contract Number:
- AC02-98CH10886
- OSTI ID:
- 1040508
- Report Number(s):
- BNL--96299-2011-JA
- Journal Information:
- PLoS ONE, Journal Name: PLoS ONE Journal Issue: 8 Vol. 6; ISSN 1932-6203
- Country of Publication:
- United States
- Language:
- English
Similar Records
Dopamine transporter gene polymorphism and psychiatric symptoms seen in schizophrenic patients at their first episode
No association between schizophrenia and polymorphisms within the genes for debrisoquine 4-hydroxylase (CYP2D6) and the dopamine transporter (DAT)
A specific haplotype at the INS/TH loci confers high susceptibility to IDDM
Journal Article
·
Fri Jul 26 04:00:00 UTC 1996
· American Journal of Medical Genetics
·
OSTI ID:539392
No association between schizophrenia and polymorphisms within the genes for debrisoquine 4-hydroxylase (CYP2D6) and the dopamine transporter (DAT)
Journal Article
·
Mon Feb 27 04:00:00 UTC 1995
· American Journal of Medical Genetics
·
OSTI ID:443802
A specific haplotype at the INS/TH loci confers high susceptibility to IDDM
Journal Article
·
Thu Sep 01 04:00:00 UTC 1994
· American Journal of Human Genetics
·
OSTI ID:134200