DBH
Dopamine beta-hydroxylase (EC 1.14.17.1) (Dopamine beta-monooxygenase) [Contains: Soluble dopamine beta-hydroxylase]
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ADHD is associated with an elevated risk of mortality and reduced estimated life expectancy (ELE) by adulthood. Reduced life expectancy is substantially related to the trait of behavioral disinhibition; a correlate of both ADHD and of several dopamine genes related to dopamine signaling and metabolism. We therefore hypothesized that several ADHD risk genes related to dopamine might also be predictive of reduced ELE. Using a longitudinal study of 131 hyperactive children and 71 control cases followed to young adulthood, we examined whether several polymorphisms involving DRD4, DAT1, and DBH were related to ELE. The homozygous 9/9 allele of DAT1 and the heterozygous allele of DBH TaqI were associated with 5- and 2-year reductions, respectively, in total ELE. They did not operate on ELE through any relationships to ADHD specifically or behavioral disinhibition more generally. Instead, they showed links to alcohol use (DBH), reduced education, smoking, and reduced exercise (DAT1) employed in the computation of ELE. We conclude that polymorphisms of two dopamine genes are linked to reductions in ELE independently of their association with ADHD.
MeSH Terms
- Adolescent
- Adult
- Alleles
- Attention Deficit Disorder with Hyperactivity
- Case-Control Studies
- Child
- Dopamine
- Dopamine Plasma Membrane Transport Proteins
- Dopamine beta-Hydroxylase
- Female
- Follow-Up Studies
- Gene Frequency
- Genetic Predisposition to Disease
- Genotype
- Humans
- Life Expectancy
- Longitudinal Studies
- Male
- Minisatellite Repeats
- Polymorphism, Genetic
- Receptors, Dopamine D4
- Risk Factors
- Young Adult
Keywords
- attention deficit hyperactivity disorder
- dopamine genes
- estimated life expectancy
- young adult follow-up
The purpose of this study was to investigate immunoreactivity for dopamine β-hydroxylase (DBH) and tyrosine hydroxylase (TH) in carotid body (CB) glomus cells in spontaneously hypertensive rats (SHR/Izm) at 4 (prehypertensive stage), 8 (early stage of developmental hypertension), 12 (later stage of developmental hypertension), and 16weeks of age (established hypertensive stage). Age-matched Wistar Kyoto rats (WKY/Izm) were used as controls. Staining properties for TH were similar between both strains at each age. Regarding DBH immunostaining, although some glomus cells showed intense DBH immunoreactivity at 4weeks of age, these cells were rarely observed at 8, 12, and 16weeks of age in WKY/Izm. In SHR/Izm, intense DBH immunoreactivity was observed in some glomus cells at 4weeks of age, these cells were also observed at 8 and 12weeks of age, and their number increased at 16weeks of age. An image analysis showed that the percentage of DBH-immunopositive glomus cells in WKY/Izm was approximately 30% at 4weeks of age and significantly decreased to approximately 10% at 8, 12, and 16weeks of age (p<0.05). This percentage in SHR/Izm was approximately 40% at each age. The gray scale intensity for DBH immunoreactivity in DBH-immunopositive glomus cells was similar in both strains at 4weeks of age, but became significantly lower in WKY/Izm and higher in SHR/Izm with increase in age (p<0.05). These results suggest that noradrenaline in glomus cells plays an important role in the regulation of neurotransmission between CB and afferent nerves during developmental hypertension.
MeSH Terms
- Aging
- Animals
- Carotid Body
- Cell Count
- Dopamine beta-Hydroxylase
- Fluorescent Antibody Technique
- Hypertension
- Male
- Neurons
- Rats, Inbred SHR
- Rats, Inbred WKY
- Tyrosine 3-Monooxygenase
Keywords
- Carotid body
- Dopamine β-hydroxylase
- Glomus cells
- Noradrenaline
- Spontaneously hypertensive rat
We hypothesized that normal variation in genes influencing the bioavailability of dopamine in prefrontal cortex contribute to inter-individual differences in working memory (WM), particularly in healthy old age. To test this, 858 healthy young, middle-aged, and older people were tested on a spatial WM task and genotyped for catechol-O-methyltransferase (COMT VAL158MET) and dopamine betahydroxylase (DBH; C-1021T) single nucleotide polymorphisms (SNPs). Since these genes encode enzymes influencing levels of extracellular dopamine, important for WM, we reasoned that individuals with low activity alleles of each SNP (less efficient degradation of dopamine by COMT and less efficient conversion of dopamine to norepinephrine by DBH) would have higher levels of extracellular dopamine and therefore better WM performance. We predicted the poorest WM performance in people who are both COMT VAL/VAL and DBH C/C homozygotes, encoding enzymes with high activity. That prediction was borne out, but only in the older group under difficult discrimination. This suggests the high activity alleles of these 2 genes combine in reducing ability to manipulate information in WM among the old. Further, we predicted the best performance in people who inherited both low activity alleles. That prediction was not borne out. That we found genetic effects only among older people and not in midlife indicates that brain changes late in life heighten negative effects of chronically lower levels of extracellular dopamine due to normal genetic variation. We found that age increased the combined effect on WM of the COMT and DBH genes encoding enzymes controlling levels of extracellular dopamine.
MeSH Terms
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Aging
- Alleles
- Catechol O-Methyltransferase
- Cognition
- Dopamine
- Female
- Genotype
- Humans
- Male
- Memory, Short-Term
- Middle Aged
- Neuropsychological Tests
- Polymorphism, Single Nucleotide
- Prefrontal Cortex
- Young Adult