Association analysis between polymorphisms in dopamine D2 receptor (DRD2) and dopamine transporter (DAT1) genes with cocaine dependence
Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. <> Neuroscience Letters
(Impact Factor: 2.03).
02/2010; 473(2):87-91. DOI: 10.1016/j.neulet.2010.02.021
Genetic research on cocaine dependence (CD) may help clarify our understanding of the disorder as well as provide novel insights for effective treatment. Since dopamine neurotransmission has been shown to be involved in drug reward, related genes are plausible candidates for susceptibility to CD. The dopamine receptor D(2) (DRD2) protein and dopamine transporter (DAT1) protein play regulatory roles in dopamine neurotransmission. The TaqI A single-nucleotide polymorphism (SNP) in the DRD2 gene and the 3' variable number tandem repeat (VNTR) polymorphism in the DAT1 gene have been implicated in psychiatric disorders and drug addictions. In this study, we hypothesize that these polymorphisms contribute to increased risk for CD. Cocaine-dependent individuals (n=347) and unaffected controls (n=257) of African descent were genotyped for the polymorphisms in the DRD2 and DAT1 genes. We observed no statistically significant differences or trends in allele or genotype frequencies between cases and controls for either of the tested polymorphisms. Our study suggests that there is no association between the DRD2 and DAT1 polymorphisms and CD. However, additional studies using larger sample sizes and clinically homogenous populations are necessary before confidently excluding these variants as contributing genetic risk factors for CD.
Available from: Helen Pettinati
- "Striatal dopamine D2 and D3 receptor binding and dopamine release have also been found to be reduced in heroin-dependent subjects when compared to healthy controls (Martinez et al., 2012). Furthermore, genetic association studies have found genetic variants in dopaminergic genes to be associated with cocaine dependence (Lohoff et al., 2010). "
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ABSTRACT: The risk for drug addiction is partially heritable. Genes of the dopamine system are likely candidates to harbour risk variants, as dopamine neurotransmission is involved in mediating the rewarding effects of drugs of abuse. One functional single nucleotide polymorphism in dopamine receptor D2 (DRD2), rs1076560, is involved in regulating splicing of the gene and alters the ratio of DRD2 isoforms located pre- and postsynaptically. rs1076560 has been previously associated with cocaine abuse and we set out to confirm this association in a sample of European American (EA) (n = 336) and African American (AA) (n = 1034) cocaine addicts and EA (n = 656) and AA (n = 668) controls. We also analysed the role of rs1076560 in opioid dependence by genotyping EA (n = 1041) and AA (n = 284) opioid addicts. rs1076560 was found to be nominally associated with opioid dependence in EAs (p = 0.02, OR = 1.27) and AAs (p = 0.03, OR = 1.43). When both opioid-addicted ancestral samples were combined, rs1076560 was significantly associated with increased risk for drug dependence (p = 0.0038, OR = 1.29). This association remained significant after correction for multiple testing. No association was found with cocaine dependence. These data demonstrate the importance of dopamine gene variants in the risk for opioid dependence and highlight a functional polymorphism that warrants further study.
Available from: Leonardo beltrán
- "In this and other studies no relationship between this polymorphism and drug dependence
were found. However most of the studies support an association of the mutated allele A with heroin abuse, alcohol, smoking and various aspects of addictive behavior
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Determine the prevalence and compare some genetic markers involved in addictive behavior in a group of addicts to derivative of coca (cocaine/crack) or heroin and a control group of non-addicted people matched for gender, age and ethnicity.
A 120 addicts and 120 non-addicts Colombian male were surveyed and genotyped for 18 polymorphism of the OPRM1, DRD2, DRD4, SLC6A3, SLC6A4, ABCB1, DβH and CYP2B6 genes. For the identification of alleles markers were used mini-sequencing and fragment multiplex PCR techniques; ethnicity of cases and controls was analyzed with 61 AIMs.
The age of onset use of heroin or coca derivatives (cocaine/crack) was 16.5±6 years and 99.2% of them consume several illicit drugs. It showed that controls and addicts belong to the same ethnic group. Significant differences between addicts and controls in relation to schooling, marital status, social security family history of substance abuse (p <0.001), Int8-VNTR SLC6A3 gene (p= 0.015) and SNP 3435C>T ABCB1 gene (p= 0.001) were found.
The present results indicate that the VNTR- 6R polymorphism of the gene SLC6A3 and the genotype 3435CC in the ABCB1 gene, are both associated with addictive behavior to heroin or cocaine.
Available from: Radek Ptacek
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ABSTRACT: Psychiatric genetics is a popular and much-discussed topic. Many candidate genes have been investigated in relation to psychiatric disorders and many connections have been found. The utilization of these investigations is currently at a theoretical level. Nevertheless, these findings of candidate genes will be important for further research and subsequent clinical use, for example in pharmacogenetics). Due to the rapidly growing number of empirical studies that provide profound analysis of different genes and their variants in different psychiatrical symptomatology, the field is highly divided, and providing a succinct overview is challenging. This article attempts to provide an up-to-date review of the most important and most discussed genes (mainly transporter and receptor genes) contributing to the etiology of psychiatric disorders.
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