Potential association of DRD2 and DAT1 genetic variation with heroin dependence.
ABSTRACT The aim of our study was to investigate the potential association of dopamine receptor D2 gene (DRD2) TaqI RFLP A (rs1800497) and dopamine transporter gene (DAT) 3'untranslated region VNTR genetic variations with heroin addiction. Genotyping was performed using PCR-based techniques in 530 heroin abusers and 500 controls. Our results showed that DRD2 TaqI A1 allele carriers (genotypes A1A1 and A1A2) were prone to heroin abuse in models of dominance or co-dominance. We detected a 12 repeat allele and 6/6, 7/9, 9/11, 10/12 genotype in a Chinese/eastern Asian population for the first time. However, no significant differences in the DAT1 VNTR were found between the two groups in either genotypic or allelic distributions and there was no gene interaction between the two genetic loci.
SourceAvailable from: Frans J Cronjé[Show abstract] [Hide abstract]
ABSTRACT: Following the first association between the dopamine D2 receptor gene polymorphism and severe alcoholism, there has been an explosion of research reports in the psychiatric and behavioral addiction literature and neurogenetics. With this increased knowledge, the field has been rife with controversy. Moreover, with the advent of Whole Genome-Wide Studies (GWAS) and Whole Exome Sequencing (WES), along with Functional Genome Convergence, the multiple-candidate gene approach still has merit and is considered by many as the most prudent approach. However, it is the combination of these two approaches that will ultimately define real, genetic allelic relationships, in terms of both risk and etiology. Since 1996, our laboratory has coined the umbrella term Reward Deficiency Syndrome (RDS) to explain the common neurochemical and genetic mechanisms involved with both substance and non-substance, addictive behaviors.Journal of Behavioural Addictions 09/2014; 3(3):149-56. DOI:10.1556/JBA.3.2014.019
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ABSTRACT: Trait theories of leadership have documented the role of individual characteristics in affecting leadership. Twin studies have further revealed significant genetic effects on leadership role occupancy. In the era of genomics, the current research examines how a dopamine transporter gene, DAT1, is involved in genetic influences on leadership role occupancy. Study 1 found DAT1 10-repeat allele to negatively relate to proactive personality, which in turn was positively associated with leadership role occupancy. The negative indirect effect was significant, but the overall relationship between this gene and leadership was not. In addition to replicating Study 1's findings using a nationally representative sample, Study 2 revealed another countervailing mechanism: DAT1 was positively related to (moderate) rule breaking, which was positively associated with leadership role occupancy. Consistent findings across the two studies suggest that the pathways linking specific genes to leadership are complex and a middle-ground approach is needed in such multidisciplinary investigations.The Leadership Quarterly 01/2015; DOI:10.1016/j.leaqua.2014.12.005 · 2.70 Impact Factor
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ABSTRACT: Obesity as a result of overeating as well as a number of well described eating disorders has been accurately considered to be a world-wide epidemic. Recently a number of theories backed by a plethora of scientifically sound neurochemical and genetic studies provide strong evidence that food addiction is similar to psychoactive drug addiction. Our laboratory has published on the concept known as Reward Deficiency Syndrome (RDS) which is a genetic and epigenetic phenomena leading to impairment of the brain reward circuitry resulting in a hypo-dopaminergic function. RDS involves the interactions of powerful neurotransmitters and results in abnormal craving behavior. A number of important facts which could help translate to potential therapeutic targets espoused in this focused review include: (1) consumption of alcohol in large quantities or carbohydrates binging stimulates the brain's production of and utilization of dopamine; (2) in the meso-limbic system the enkephalinergic neurons are in close proximity, to glucose receptors; (3) highly concentrated glucose activates the calcium channel to stimulate dopamine release from P12 cells; (4) a significant correlation between blood glucose and cerebrospinal fluid concentrations of homovanillic acid the dopamine metabolite; (5) 2-deoxyglucose (2DG), the glucose analog, in pharmacological doses is associated with enhanced dopamine turnover and causes acute glucoprivation. Evidence from animal studies and fMRI in humans support the hypothesis that multiple, but similar brain circuits are disrupted in obesity and drug dependence and for the most part, implicate the involvement of DA-modulated reward circuits in pathologic eating behaviors. Based on a consensus of neuroscience research treatment of both glucose and drug like cocaine, opiates should incorporate dopamine agonist therapy in contrast to current theories and practices that utilizes dopamine antagonistic therapy. Considering that up until now clinical utilization of powerful dopamine D2 agonists have failed due to chronic down regulation of D2 receptors newer targets based on novel less powerful D2 agonists that up-regulate D2 receptors seems prudent. We encourage new strategies targeted at improving DA function in the treatment and prevention of obesity a subtype of reward deficiency.Frontiers in Psychology 09/2014; 5:919. DOI:10.3389/fpsyg.2014.00919 · 2.80 Impact Factor