Table 2 Effects of gene variants
Gene variant | Gene product | Gene product function | Influence of variant | Primary brain regions of action | Physiologic effects |
|---|---|---|---|---|---|
Dopamine system | Â | Â | Â | Â | Â |
COMT (Val158Met) | Catechol-o-methyltransferase | Degradation of catecholamines | Met variant- carriers have reduced COMT activity | Prefrontal Cortex | Differential dopaminergic signaling influences PFC function (COMT-genotype model), may explain different drug effects [58] |
DRD4 (exon 3 VNTR) | Dopamine receptor D4 | Dopaminergic transmission | 7R-carriers have reduced DRD4 function | Prefrontal Cortex | Variation in dopaminergic signaling influences PFC function, interaction with other genotypes [25] |
SLC6A3 (3′UTR VNTR); SLC6A3 (3′UTR VNTR/intron 8 VNTR haplotype) | Dopamine transporter | Reuptake of dopamine | 9R- vs. 10R-carriers have reduced or increased DAT availability (inconsistent findings) | Striatum | Variability of striatal dopamine Transporter availability influences PFC function directly or indirectly via cortico-striatal pathways [24] |
Serotonin system | Â | Â | Â | Â | Â |
TPH2 (e.g. rs4570625, rs11178997) | Tryptophan hydroxylase 2 | Synthesis of serotonin | Influences transcriptional activity | Raphe nuclei, with ubiquitous action of serotonin | Differential activity of the cortico-limbic circuit |
Others | Â | Â | Â | Â | Â |
NOS1 exon 1f-VNTR | Neuronal nitric oxide (NO) synthase | Synthesis of neuronal NO | Allelic variation in reporter gene expression | Striatum | NO function influences dopamine signaling [32] |
LPHN3 (ADHD risk haplotype) | Latrophilin | Adhesion G-protein coupled receptor (?) | Decreased NAA/Cr ratio in risk haplotype carriers | Amygdala, caudate nucleus, cerebellum, and cerebral cortex | Possibly influences dopamine-glutamatergic system interaction |