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Table 2 Effects of gene variants

From: Imaging genetics in adult attention-deficit/hyperactivity disorder (ADHD): a way towards pathophysiological understanding?

Gene variant Gene product Gene product function Influence of variant Primary brain regions of action Physiologic effects
Dopamine system      
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      
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
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
  1. COMT, Catechol-o-methyltransferase; DAT, dopamine transporter; NAA/Cr, N-acetyl aspartate/creatine; NO, nitric oxide; PFC, prefrontal cortex; UTR, untranslated region; VNTR, variable number of tandem repeats.