Dopamine D1, D2 and D3 receptor genes in alcohol dependence

Sander, Thomas; Harms, Helmut; Podschus, Jan; Finckh, Ulrich; Nickel, B; Rolfs, Arndt; Rommelspacher, H.; Schmidt, L. G.

doi:10.1097/00041444-199524000-00004

Cited by 90 publications

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“…Sander et al [23] also reported an increased frequency of the S allele in AD patients with delirium. The results of the present study therefore show trends of association that differ from those of previous studies with positive findings.…”

Section: Discussionmentioning

confidence: 99%

“…Studies involving French, German and Japanese subjects have yielded negative findings [7,19,20,21]. In contrast, another German study found a significant association between this polymorphism and AD [22], and the results of an earlier study suggested an increased frequency of allele 1 (S allele) in AD patients with delirium [23]. A previous Korean study has also yielded negative findings; however, that study involved only a small number of subjects for the genetic association study (67 AD subjects vs. 67 controls) [24].…”

Section: Introductionmentioning

confidence: 99%

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DRD3 Gene rs6280 Polymorphism May Be Associated with Alcohol Dependence Overall and with Lesch Type I Alcohol Dependence in Koreans

Kang

Lee

Lee³

et al. 2014

Neuropsychobiology

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Background: Several polymorphisms of the dopamine D₃ receptor (DRD3) gene are reported to be involved in the susceptibility to alcoholism. Although the DRD3 rs6280 (Ser9Gly) polymorphism plays an important role in various psychiatric disorders, findings regarding the association between this single-nucleotide polymorphism (SNP) and alcohol dependence (AD) have been inconsistent. Therefore, the present study investigated the association between the DRD3 gene rs6280 polymorphism with AD and Lesch type I AD in Korean subjects. Methods: The DRD3 rs6280 SNP was genotyped in a case-control sample comprising 245 AD patients and 130 healthy controls (HCs). Alcohol Use Disorders Identification Test (AUDIT) scores were also compared relative to genotype in all of the participants. Results: This SNP was significantly associated with both AD overall (χ² = 10.09 and p = 0.001, and χ² = 10.60 and p = 0.005, for the recessive and additive models, respectively) and with Lesch type I AD (χ² = 11.70 and p = 0.001, and χ² = 11.70 and p = 0.003, for the recessive and additive models, respectively). The allele frequency differed significantly (χ² = 8.45, p = 0.004) between Lesch type I AD and HC subjects. The AUDIT total (F = 6.56, p = 0.011), hazardous alcohol use (F = 7.12, p = 0.008), dependence symptoms (F = 5.10, p = 0.025), and harmful alcohol use (F = 4.83, p = 0.029) scores were significantly higher in those who did not possess the S allele (genotype GG) than in those who did (genotypes SS ± SG). Conclusions: The findings of this study suggest that the DRD3 rs6280 polymorphism is associated with the development of both AD overall and Lesch type I AD in Koreans.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

DRD3 Gene rs6280 Polymorphism May Be Associated with Alcohol Dependence Overall and with Lesch Type I Alcohol Dependence in Koreans

Kang

Lee

Lee³

et al. 2014

Neuropsychobiology

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“…[26][27][28] Alcohol-only users thus resemble opiate addicts with low sensation-seeking scores, who did not differ from controls with respect to DRD3 genotypes. On the other hand, association between DRD3 and schizophrenia has also been reported, but there is a much higher proportion of drug addicts among schizophrenic patients (35-40%) than in the general population.…”

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confidence: 92%

Homozygosity at the dopamine D3 receptor gene is associated with opiate dependence

et al. 1998

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Anatomical, pharmacological and human post-mortem studies suggest the dopamine D 3 receptor (DRD3) gene as a candidate for drug dependence. We thus performed an association study of the Bal I polymorphism at the DRD3 gene, including 54 opiate addicts and 70 controls. Opiate addicts had a higher sensation-seeking score (on the Zü ckerman scale) than controls (P = 0.001), particularly a subgroup (70%) who had a distinctly higher score, exceeding 24. There were no marked differences in genotypes between patients as a whole and controls. However, patients with a sensation-seeking score above 24 were more frequently homozygotes for both alleles than patients with a sensation-seeking score under 24 (P = 0.038) or controls (P = 0.034). Although obtained in a sample of limited size, these results suggest that the DRD3 gene may have a role in drug dependence susceptibility in individuals with high sensation-seeking scores. This hypothesis is consistent with the role of DRD3 in mediating responses to drugs of abuse in animals and the association of homozygosity at the Bal I polymorphism with drug abuse in schizophrenic patients (see companion article by Krebs et al).Addiction to substances, including drugs and alcohol, probably arises from a combination of environmental and genetic factors. 1-3 Alcohol, opiates and psychostimulants share the ability in animals to enhance the activity of mesolimbic-mesocortical dopaminergic neurons, thought to be involved in drug reward and reinforcement. 4 The dopamine D 3 receptor (DRD3) is selectively expressed in the projection field of dopaminergic mesolimbic-mesocortical neurons. 5 Stimulation of DRD3 enhances the reinforcing properties of cocaine in rats 6 and monkeys; 7,8 behavioral sensitization occurring after repeated administration of an indirect dopamine agonist, a process also observed after repeated administration of opiates and psychostimulants, is accompanied by a selective induction of DRD3 gene expression. 9 Furthermore, DRD3 binding 10 and gene transcripts 11 are elevated in the ventral striatum of cocaine fatalities. These experimental and clinical observations suggest the DRD3 gene as a candidate for susceptibility to drug dependence.We recruited 54 patients with opiate dependence and without schizophrenia, both according to DSM-III-R criteria (mean age ± s.d. 32.3 ± 6.1 yrs), and 70 controls without drug use or any psychiatric disease (mean age 42.2 ± 7 yrs), all white males of French ancestry. The older age of controls minimises the risk of including not yet revealed addicts. Twenty-nine patients had less than three life-time comorbid substance dependences, and 25 more than three comorbid dependences. The age of first opiate use was 18.6 ± 2.9 yrs.The sensation-seeking score, as assessed using the Zü ckerman scale, was significantly higher in patients (26 ± 5) than in controls (17 ± 6, P = 0.001). The sensation-seeking score in patients was found inversely correlated with age (r = −0.37, P = 0.005), as it is in the general population. 12 However, testing for normali...

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“…10 Therefore, the DRD3 gene appears as a candidate gene not only for schizophrenia, but also for alcoholism and/or drug addiction, in which the influence of genetic factors has also been established. 11 Association studies in alcoholism have led to contradictory results [12][13][14] but, in an accompanying paper, homozygozity at the DRD3 gene Bal I polymorphism was associated with opiate abuse. 15 The present study reports a positive association of homozygozity of DRD3 gene at Bal I polymorphism in a French sample of schizophrenic patients with current or past substance abuse comorbidity and in patients who respond to neuroleptic treatment.…”

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Dopamine D3 receptor gene variants and substance abuse in schizophrenia

et al. 1998

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In an association study of the Bal I polymorphism in the dopamine D 3 receptor (DRD3) gene in a French Caucasian population, global comparison of patients with schizophrenia (n = 89, DSM-III-R criteria) and controls (n = 52) led to non-significant differences. However, the homozygosity was significantly more frequent in schizophrenic patients with lifetime substance abuse comorbidity (n = 36) as compared to patients with no history of substance abuse (P = 0.010) or to controls (P = 0.047) and in neuroleptic responder patients as compared to treatment-refractory patients (n = 19; P = 0.037). The combined characteristics treatment response and lifetime substance abuse were strongly associated with homozygosity. We propose that homozygosity for the Bal I polymorphism DRD3 gene is associated with predisposition to substance abuse and/or the pharmacosensitive characteristic of schizophrenia rather than with schizophrenia itself, an hypothesis in agreement with the positive association of this polymorphism with opiate dependence (see companion article by Duaux et al) and the involvement of DRD3 in both pharmacodependence mechanisms and antipsychotic effects of neuroleptics.

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Dopamine D1, D2 and D3 receptor genes in alcohol dependence

Cited by 90 publications

References 0 publications

DRD3 Gene rs6280 Polymorphism May Be Associated with Alcohol Dependence Overall and with Lesch Type I Alcohol Dependence in Koreans

DRD3 Gene rs6280 Polymorphism May Be Associated with Alcohol Dependence Overall and with Lesch Type I Alcohol Dependence in Koreans

Homozygosity at the dopamine D3 receptor gene is associated with opiate dependence

Dopamine D3 receptor gene variants and substance abuse in schizophrenia

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