Potential association of DRD2 and DAT1 genetic variation with heroin dependence. Neuroscience Letters
Key Laboratory of the National Ministry of Health for Forensic Sciences, College of Medicine, Xi'an Jiaotong University, 76 Yanta West Road, Xi'an 710061, PR China. Neuroscience Letters
(Impact Factor: 2.03).
09/2009; 464(2):127-30. DOI: 10.1016/j.neulet.2009.08.004
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.
Available from: Wendong Li
- "In the sample, 83.8% of the participants had two homozygous 10-repeat alleles, 12.6% had one 10- repeat allele, and 3.6% had no 10-repeat alleles. The distribution of 10-repeat alleles was similar to that reported in previous studies (Cheuk, Li, & Wong, 2006; Hou & Li, 2009; Qian et al., 2007). "
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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.
Available from: Kenneth Blum
- "Since that time there have been no less than 3738 (Pubmed-6-23-14) peer reviewed articles on many peripheral and central nervous system (CNS) behaviors and physiological processes. Understandably addiction or even the broader term RDS involves very complex gene × environment interaction and one cannot expect that a single gene like the DRD2 gene would have a powerful effect by itself, however, albeit many negative findings, there is still a plethora of evidence for the role of the DRD2 gene polymorphisms and a number (small sample of studies represented herein) of addictive and other reward dependent behaviors including: alcohol dependence (Pato et al., 1993; Ponce et al., 2003; Munafò et al., 2007; Smith et al., 2008; Pinto et al., 2009; Grzywacz et al., 2012; Wang et al., 2013); drug dependence (Li et al., 2004; Xu et al., 2004; Young et al., 2004; Barratt et al., 2006; Li et al., 2006; Hou and Li, 2009; Chen et al., 2011a,b; Al-Eitan et al., 2012; Jacobs et al., 2013; Lee et al., 2013; Ohmoto et al., 2013; Sullivan et al., 2013; Suraj Singh et al., 2013; Vereczkei et al., 2013; Wang et al., 2013; Clarke et al., 2014; Roussotte et al., 2014; Schuck et al., 2014); mood disorders (Vaske et al., 2009; Huertas et al., 2010; Zhu et al., 2011; Zou et al., 2012; Hettinger et al., 2012; Jutras-Aswad et al., 2012; Tsuchimine et al., 2012; Whitmer and Gotlib, 2012; Zai et al., 2012; Peciña et al., 2013; Zhang et al., 2014); rearing behaviors (Mills-Koonce et al., 2007; Bakermans-Kranenburg and van Ijzendoorn, 2011; Beaver and Belsky, 2012; Masarik et al., 2014); obesity (Spangler et al., 2004; Fang et al., 2005; Huang et al., 2005; Epstein et al., 2007; Nisoli et al., 2007; Barnard et al., 2008; Blum et al., 2008; Eny et al., 2009; Epstein et al., 2010; Mathes et al., 2010; Stice et al., 2010; van Strien et al., 2010; Jabłoński, 2011; Anitha et al., 2012; Chen et al., 2012; Winkler et al., 2012; Ariza et al., 2013; Carpenter et al., 2013; Cameron et al., 2013; Hess et al., 2013; Alsiö et al., 2014); Anorexia Nervosa (Bergen et al., 2005); motivation (Trifilieff et al., 2013); brain metabolism (Noble et al., 1997); ADHD (Gold et al., 2014), and pathological gambling (Gyollai et al., 2014). "
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ABSTRACT: Obesity and many well described eating disorders are accurately considered a global epidemic. The consequences of Reward Deficiency Syndrome, a genetic and epigenetic phenomena that involves the interactions of powerful neurotransmitters, are impairments of brain reward circuitry, hypodopaminergic function and abnormal craving behavior. Numerous sound neurochemical and genetic studies provide strong evidence that food addiction is similar to psychoactive drug addiction. Important facts which could translate to potential therapeutic targets espoused in this review include: 1) brain dopamine (DA) production and use is stimulated by consumption of alcohol in large quantities or carbohydrates bingeing; 2) in the mesolimbic 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) blood glucose and cerebrospinal fluid concentrations of homovanillic acid, the dopamine metabolite, are significantly correlated and 5) 2-deoxyglucose the glucose analogue, in pharmacological doses associates with enhanced dopamine turnover and causes acute glucoprivation. Evidence from animal studies and human fMRI support the hypothesis that multiple, but similar brain circuits are disrupted in obesity and drug dependence and DA-modulated reward circuits are involved in pathologic eating behaviors. Treatment for addiction to glucose and drugs alike, based on a consensus of neuroscience research, should incorporate dopamine agonist therapy, in contrast to current theories and practices that use dopamine antagonists. Until now, powerful dopamine-D2 agonists have failed clinically, due to chronic down regulation of D2 receptors instead, consideration of 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.
Available from: Liang-Jen Wang
- "This polymorphism has revealed associations with alcoholism (Bhaskar, Thangaraj, Wasnik, Singh, & Raghavendra Rao, 2012) and neurotoxicity effect of amphetamine (Giros, Jaber, Jones, Wightman, & Caron, 1996). However, the relationships between allele frequency of DAT1 3 -UTR VNTR and heroin dependence are unclear (Hou & Li, 2009; Yeh et al., 2010). Furthermore, little is known about whether the DAT1 3 -UTR VNTR contributes to the pathogenesis of drug-related psychiatric disorders. "
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ABSTRACT: To investigate the involvement of COMT Val158Met and DAT1 3'-UTR VNTR genotypes in the pathogenesis of illicit drug use and drug-induced psychotic disorders (DIP), 187 substance users and 386 normal controls were recruited from Northern Taiwan. Substance users and normal controls significantly differed in allele frequencies of COMT Val158Met (p = 0.039) but not in allele frequencies of DAT1 3'-UTR VNTR (p = 0.879). However, neither allele frequencies of COMT Val158Met nor allele frequencies of DAT1 3'-UTR VNTR were associated with DIP. The findings should be confirmed in further studies of a larger sample size and a more homogenous patient group.
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