The brain’s dopamine system is highly complex, and is critically involved in many extremely important processes such as motivation, reward, mood, and pleasure. Because it is so complex, there is a large number of different genes and genetic variants that can potentially affect how the dopamine system works. Read on to learn about these important genetic factors, and how they can potentially affect the overall levels and activity of dopamine in the brain!
Genes and SNPs Related to Dopamine Function
1) Dopamine Receptor Genes
Dopamine receptors are how the actual neurotransmitter dopamine affects the activity of cells in the brain.
The dopamine system is highly complex, and involves many different specific types of dopamine receptors. Each type is located on particular types of neurons, and has specific individual functions that vary between the different receptor types.
Each type of receptor also has specific genes that are involved in producing the receptor, which can affect how many of each type a given person has throughout their brain, as well as exactly how they function.
Dopamine D1 Receptor gene (DRD1)
This gene encodes D1 dopamine receptors, which are believed to be involved in controlling neuronal growth and behavior [1].
Dopamine D2 Receptor gene (DRD2)
This gene encodes the “D2” type of dopamine receptor.
The ‘A’ allele of the rs1800497 SNP in the DRD2 gene has been associated with relatively reduced numbers of D2 receptors [2].
According to one study, this genetic variant may also be associated with relatively lower rates of ADHD [3].
Dopamine D3 Receptor gene (DRD3)
DRD3 encodes dopamine receptors that are located in the limbic areas of the brain, which have been associated with a wide variety of cognitive, emotional, and hormonal functions [4].
Dopamine D4 Receptor gene (DRD4) [5]
Dopamine D5 Receptor gene (DRD5)
2) Dopamine Production, Breakdown, and Conversion
Just as there are many different types of receptors that dopamine can bind to influence neural activity throughout the brain, there is also a large number of specific compounds involved in producing the neurotransmitter dopamine itself.
Similarly, there are a number of different genes involved in creating the various “ingredients” (metabolic precursors) and other compounds necessary for creating dopamine in the brain. Variants in these genes can influence how much dopamine an individual creates.
Relatedly, there are also many other compounds that help break down (metabolize) dopamine, which makes it inactive. Variants in the genes that help create these compounds can also have a significant effect on how much active dopamine a given person has throughout their brain.
Tyrosine Hydroxylase (TH)
The TH protein is responsible for stimulating the creation (chemical synthesis) of dopamine. Specifically, it is involved in the conversion of tyrosine into dopamine [6].
Dopamine beta-hydroxylase (DBH)
DBH is involved in converting dopamine into norepinephrine (also known as “noradrenaline”) [7].
Catechol-O-Methyltransferase (COMT)
COMT is an enzyme that breaks down (metabolizes) dopamine – especially in parts of the brain that are responsible for cognitive or executive functions (such as the prefrontal cortex) [8].
A well-studied SNP in COMT (rs4680) affects dopamine levels, and results in different personality traits. Read more about it here.
D-amino acid oxidase (DAO)
DAO contributes to the creation (synthesis) of dopamine [9].
DOPA decarboxylase (DDC)
DDC helps with the conversion of L-DOPA into dopamine. It is part of the pathway that produces dopamine and serotonin [10].
Monoamine oxidase A (MAOA)
MAOA is an enzyme that breaks down dopamine [11].
Monoamine oxidase B (MAOB)
MAOB is an enzyme that breaks down dopamine [11].
Cholinergic receptor nicotinic alpha 4 subunits (CHRNA4)
CHRNA4 encodes a protein that is involved in the control of dopamine synthesis [12].
Cholinergic receptor nicotinic beta 2 subunits (CHRNB2)
CHRNB2 encodes a protein that is involved in the positive control of dopamine synthesis [13].
Dystrobrevin binding protein 1 (DTNBP1)
DTNBP1 encodes a protein that is involved in the control of dopamine synthesis [14].
Fibroblast growth factor 20 (FGF20)
FGF20 encodes a protein that is involved in the process of dopamine synthesis [15].
5-hydroxytryptamine receptor 2A (HTR2A or 5-HT2A)
HTR2A, a serotonin receptor, is involved in the process of dopamine synthesis [16].
5-hydroxytryptamine receptor 1A (HTR1A or 5-HT1A)
HTR1A is believed to play a role in stimulating the release of dopamine throughout the medial prefrontal cortex, striatum, and hippocampus. Some researchers have proposed that this gene may be involved in the development of certain psychiatric or neurological disorders, such as schizophrenia and Parkinson’s disease [17].
5-hydroxytryptamine receptor 1B (HTR1B)
HTR1B is a protein that is believed to be involved in inhibiting the release of dopamine in the prefrontal cortex [18].
Parkin RBR E3 ubiquitin protein ligase (PRKN)
PRKN is involved in the creation of dopamine, as well as its breakdown (metabolism). It may also play a role in how cells absorb (uptake) dopamine, as well as how they release (secrete) it [19].
Parkinsonism-associated deglycase (PARK7)
PARK7 is believed to be involved in stimulating the creation (synthesis) of dopamine [20].
Synuclein alpha (SNCA)
SNCA is believed to be responsible for inhibiting the cellular uptake and release of dopamine [21].
Angiotensin II receptor type 2 (AGTR2)
AGTR2 is believed to be involved in the creation of dopamine [22].
GTP cyclohydrolase 1 (GCH1)
GCH1 is also believed to be involved in the creation of dopamine [23].
G protein-coupled receptor 37 (GPR37)
GPR37 is believed to affect the activity of the dopamine transporter, the molecule that helps cells absorb (uptake) dopamine from the synapse so that it can be re-used [24].
Transforming growth factor beta 2 (TGFB2)
TGFB2 is involved in the creation of dopamine [25].
PTEN induced putative kinase 1 (PINK1)
PINK1 is believed to stimulate the release (secretion) of dopamine from neurons [26].
Neuropeptide Y receptor Y2 (NPY2R)
NPY2R is believed to be involved in stimulating dopamine production [27].
4-aminobutyrate aminotransferase (ABAT)
ABAT has been proposed to have two different roles that effectively reduce dopamine activity in the brain. Firstly, it may inhibit the release (secretion) of dopamine from neurons. Secondly, it may stimulate the break-down (metabolism) of dopamine from an active state into an inactive state [28].
Monooxygenase DBH-like 1 (MOXD1)
MOXD1 is involved in breaking down dopamine [29].
3) Genes Involved with Dopamine Binding
Adrenoceptor beta 2 (ADRB2)
Variants in the ADRB2 gene are believed to affect how dopamine binds to its receptors throughout the brain [30].
G protein-coupled receptor 143 (GPR143)
GPR143 is also believed to be involved in dopamine binding. It is also a receptor for tyrosine, L-DOPA, and dopamine [31].
4) Genes Involved with Dopamine Transport
After neurotransmitters are released by brain cells, they have to be brought back into the neuron so that they can be “re-used” again.
The “helper molecules” that help bring neurotransmitters back into neurons are called transporters. There are different transporter molecules for different types of neurotransmitters, and also have their own genes that help to produce them.
Genes that affect the levels and activity of these transporters can also have a significant effect on neurotransmitter levels and activity throughout the brain as a whole.
Solute carrier family 22 member 1 (SLC22A1)
SLC22A1 encodes for a protein involved in dopamine transport [32].
Solute carrier family 22 member 2 (SLC22A2)
SLC22A2 encodes for a protein involved in dopamine transport [33].
Solute carrier family 22 member 3 (SLC22A3)
SLC22A3 encodes for a protein involved in dopamine transport [34].
Solute carrier family 6 member 3 (SLC6A3)
SLC6A3 encodes a protein called dopamine transporter (DAT), which – as its name suggests – transports dopamine into the cell [35].
Vesicular monoamine transporter 2 (VMAT2)
VMAT2 is a protein encoded by the SLC18A2 gene. It is involved in dopamine transport [36].
Torsin family 1 member A (TOR1A)
TOR1A controls the location of dopamine transporter SLC6A3, which is also believed to give it a (slightly indirect) role in controlling dopamine activity [22].
