The DRD2 A1 allele was present in 73.9% of the obese subjects with comorbid substance use disorder compared to 23.5% in obese subjects without comorbid substance use disorder.
The identification of phenotypes of DRD2 genotypes suggests that the observed intronic DRD2 mutations may have functional consequences that predispose individuals to a variety of substance use disorders.
Because the D2 dopamine receptor (DRD2) A1 allele has been associated with alcoholism and other substance use disorders, negative affect, measured by the Beck Depression Inventory (BDI), was determined in four groups of children: boys and girls with the A1+ allele (A1A1 and A1A2 genotypes) and with the A1- allele (A2A2 genotype).
A total of 110 adult patients with ASD (n=61) or ADHD (n=49) with or without a lifetime history of SUD participated in a study in which we genotyped polymorphisms in five known candidate genes for (one of) the disorders, i.e. the 5HTTLPR in SLC6A4/5-HTT, rs1800497 (TaqIA C>T) in DRD2, rs7794745 in CNTNAP2, rs1843809 in TPH2, and rs6565113 in CDH13.
In the presented study, one of selected polymorphisms of DRD2 gene, revealed to be correlated with substance use disorder (at the limit of statistical significance), which could suggest its impact on dependence endophenotype.
We hypothesize that dopamine D2 receptor (DRD2) gene Taq1 A2 allele is associated with a subtype of non-SUD schizophrenics and as such may act as a putative protective agent against the development of addiction to alcohol or other drugs of abuse.
However, a meta-analysis of a large number of Caucasian alcoholics (both more severe and less severe) and controls (both assessed and unassessed for substance use disorders) revealed a significantly higher frequency (p < 10(-6)) and prevalence (p < 10(-8)) of the DRD2 A1 allele in the alcoholics.
Analysis of the available data suggests that the DRD2 variants represent one of the most prominent single-gene determinants of susceptibility to severe alcoholism and other substance use disorders.
Furthermore, sib pair analysis incorporating information across all three sib pair categories: concordant affected, discordant and concordant unaffected revealed no effect of DRD2 genotype or haplotype on alcoholism or substance use disorder.
If music causes a powerful activation in spite of the DRD2 A1 allele due to a strong DA neuronal release which subsequently impinges on existing D2 receptors, then it is reasonable to assume that music is a strong indirect D2 agonist (by virtue of DA neuronal release in the NAc) and may have important therapeutic applicability in Reward Deficiency Syndrome (RDS) related behaviors including Substance Use Disorder (SUD).Ross et al.
Imaging gene-substance interactions: the effect of the DRD2 TaqIA polymorphism and the dopamine agonist bromocriptine on the brain activation during the anticipation of reward.