DRD3 variation associates with early-onset heroin dependence, but not specific personality traits

Kuo, Shin-Chang; Yeh, Yi‐Wei; Chen, Chun‐Yen; Huang, Chia‐Luen; Chang, Hsin‐An; Yen, Che-Hung; Ho, Pei‐Shen; Liang, Chih‐Sung; Chou, Han-Wei; Lu, Ru‐Band; Huang, San-Yuan

doi:10.1016/j.pnpbp.2013.12.018

Cited by 30 publications

(24 citation statements)

References 72 publications

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“…In the current sample of 148 individuals, the distribution of genotypes (Ser/Ser = 71, Ser/Gly = 59, and Gly/Gly = 18) showed no deviation from Hardy-Weinberg equilibrium (χ 2 = 1.08, p = 0.30). The genotype frequencies were similar to those found in East Asian samples [26,33]. …”

Section: Methodssupporting

confidence: 84%

Investigating the Genetic Basis of Social Conformity: The Role of the Dopamine Receptor 3 (DRD3) Gene

Zhao

Liu²,

Gong

et al. 2016

Neuropsychobiology

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Background: People often change their opinions or behavior to match the responses of others, a phenomenon known as social conformity. Conforming behavior varies substantially across individuals. However, little is known about the genetic basis underlying individual differences in social conformity. A recent study demonstrated an association between enhanced dopaminergic function and increased conforming behavior. Given the effect of the dopamine receptor 3 gene (DRD3) Ser9Gly polymorphism (rs6280) on dopamine release in the striatum, this study investigated to what extent this polymorphism affects conforming behavior. Methods: We categorized Han Chinese individuals according to the polymorphism and tested them with a facial-attractiveness rating task. Results: We found that individuals with a greater number of the Gly alleles, which are related to an increased dopamine release in the striatum, were more susceptible to social influence and more likely to change their ratings to match those of other people. Conclusions: This finding demonstrates the importance of DRD3 Ser9Gly as a genetic basis for social conformity and in predicting individual differences in social learning.

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Section: Methodssupporting

confidence: 84%

Investigating the Genetic Basis of Social Conformity: The Role of the Dopamine Receptor 3 (DRD3) Gene

Zhao

Liu²,

Gong

et al. 2016

Neuropsychobiology

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“…A recent study suggests an association of a DRD3 haplotype block, specifically with early-onset heroin addiction, in Han Chinese [59]. There are no previous reports on the two DRD3 intronic SNPs indicated in this study and the p-values for two of the SNPs may be affected by their low MAF.…”

Section: Discussionmentioning

confidence: 63%

Dopaminergic Pathway Polymorphisms and Heroin Addiction: Further Support for Association of CSNK1E variants

et al. 2014

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Background & aim The dopaminergic pathways have been implicated in the etiology of drug addictions. The aim of this study was to determine if variants in dopaminergic genes are associated with heroin addiction. Materials & methods The study includes 828 former heroin addicts and 232 healthy controls, of predominantly European ancestry. Ninety seven SNPs (13 genes) were analyzed. Results Nine nominally significant associations were observed at CSNK1E, ANKK1, DRD2 and DRD3. Conclusion The results support our previous report of association of CSNK1E SNP rs1534891 with protection from heroin addiction. CSNK1E interacts with circadian rhythms and DARPP-32 and has been implicated in negative regulation of sensitivity to opioids in rodents. It may be a target for drug addiction treatment.

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“…A relatively small number of human genetic studies have investigated the association of DRD3 polymorphisms with substance and behavioral addictions, with most candidate gene studies being conducted in small samples. Recently, studies on larger ethnically homogeneous samples have reported significant associations of a number of DRD3 polymorphisms with nicotine (45,46) , opioid (47) , and alcohol addiction (48) .…”

Section: Human and Pre-clinical Findings On Dopamine D3 Gene/ Receptomentioning

confidence: 99%

Addiction-related genes in gambling disorders: new insights from parallel human and pre-clinical models

et al. 2014

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Neurobiological research supports the characterization of disordered gambling (DG) as a behavioral addiction. Recently, an animal model of gambling behavior was developed (rat gambling task, rGT), expanding the available tools to investigate DG neurobiology. We investigated whether rGT performance and associated risk gene expression in the rat's brain could provide cross-translational understanding of the neuromolecular mechanisms of addiction in DG. We genotyped tagSNPs (single-nucleotide polymorphisms) in 38 addiction-related genes in 400 DG and 345 non-DG subjects. Genes with P<0.1 in the human association analyses were selected to be investigated in the animal arm to determine whether their mRNA expression in rats was associated with the rat's performance on the rGT. In humans, DG was significantly associated with tagSNPs in DRD3 (rs167771) and CAMK2D (rs3815072). Our results suggest that age and gender might moderate the association between CAMK2D and DG. Moderation effects could not be investigated due to sample power. In the animal arm, only the association between rGT performance and Drd3 expression remained significant after Bonferroni correction for 59 brain regions. As male rats were used, gender effects could not be investigated. Our results corroborate previous findings reporting the involvement of DRD3 receptor in addictions. To our knowledge, the use of human genetics, pre-clinical models and gene expression as a cross-translation paradigm has not previously been attempted in the field of addictions. The cross-validation of human findings in animal models is crucial for improving the translation of basic research into clinical treatments, which could accelerate neurobiological and pharmacological investigations in addictions.

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DRD3 variation associates with early-onset heroin dependence, but not specific personality traits

Cited by 30 publications

References 72 publications

Investigating the Genetic Basis of Social Conformity: The Role of the Dopamine Receptor 3 <b><i>(DRD3)</i></b> Gene

Investigating the Genetic Basis of Social Conformity: The Role of the Dopamine Receptor 3 <b><i>(DRD3)</i></b> Gene

Dopaminergic Pathway Polymorphisms and Heroin Addiction: Further Support for Association of CSNK1E variants

Addiction-related genes in gambling disorders: new insights from parallel human and pre-clinical models

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