KCNJ6 is associated with adult alcohol dependence and involved in gene × early life stress interactions in adolescent alcohol drinking.
- Authors
- Clarke, Toni-Kim; Laucht, Manfred; Ridinger, Monika; Wodarz, Norbert; Rietschel, Marcella; Maier, Wolfgang; Lathrop, Mark; Lourdusamy, Anbarasu; Zimmermann, Ulrich S; Desrivieres, Sylvane; Schumann, Gunter
- Year
- 2011
- Journal
- Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
- PMID
- 21307845
- DOI
- 10.1038/npp.2010.247
- PMCID
- PMC3079832
Alcohol abuse and dependence have proven to be complex genetic traits that are influenced by environmental factors. Primate and human studies have shown that early life stress increases the propensity for alcohol abuse in later life. The reinforcing properties of alcohol are mediated by dopaminergic signaling; however, there is little evidence to indicate how stress alters alcohol reinforcement. KCNJ6 (the gene encoding G-protein-coupled inwardly rectifying potassium channel 2 (GIRK2)) is a brain expressed potassium channel with inhibitory effects on dopaminergic tone. The properties of GIRK2 have been shown to be enhanced by the stress peptide corticotrophin-releasing hormone. Therefore, we sought to examine the role of KCNJ6 polymorphisms in adult alcohol dependence and stress-related alcohol abuse in adolescents. We selected 11 SNPs in the promoter region of KCNJ6, which were genotyped in 1152 adult alcohol dependents and 1203 controls. One SNP, rs2836016, was found to be associated with alcohol dependence (p=0.01, false discovery rate). We then assessed rs2836016 in an adolescent sample of 261 subjects, which were characterized for early life stress and adolescent hazardous drinking, defined using the Alcohol Use Disorders Identification Test (AUDIT), to examine gene-environment interactions. In the adolescent sample, the risk genotype of rs2836016 was significantly associated with increased AUDIT scores, but only in those individuals exposed to high levels of psychosocial stress in early life (p=0.01). Our findings show that KCNJ6 is associated with alcohol dependence and may moderate the effect of early psychosocial stress on risky alcohol drinking in adolescents. We have identified a candidate gene for future studies investigating a possible functional link between the response to stress and alcohol reinforcement.
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| A critical review of ethanol effects on neuronal firing: A metabolic perspective. | Popova D et al. | — | 2024 | → |
| Direct modulation of G protein-gated inwardly rectifying potassium (GIRK) channels. | Nguyen H et al. | — | 2024 | → |
| Alcohol reverses the effects of KCNJ6 (GIRK2) noncoding variants on excitability of human glutamatergic neurons. | Popova D et al. | — | 2023 | → |
| Computational prognostic evaluation of Alzheimer's drugs from FDA-approved database through structural conformational dynamics and drug repositioning approaches. | Hassan M et al. | — | 2023 | → |
| Potassium Channels in Parkinson's Disease: Potential Roles in Its Pathogenesis and Innovative Molecular Targets for Treatment. | Chen X et al. | — | 2023 | → |
| Neuronal G protein-gated K<sup>+</sup> channels. | Luo H et al. | — | 2022 | → |
| Pharmacogenetics of Addiction Therapy. | Graham DP et al. | — | 2022 | → |
| Sex differences in electrophysiological properties and voltage-gated ion channel expression in the paraventricular thalamic nucleus following repeated stress. | Corbett BF et al. | — | 2022 | → |
| Single Prolonged Stress Reduces Intrinsic Excitability and Excitatory Synaptic Drive Onto Pyramidal Neurons in the Infralimbic Prefrontal Cortex of Adult Male Rats. | Nawreen N et al. | — | 2021 | → |
| Single Prolonged Stress Reduces Intrinsic Excitability and Excitatory Synaptic Drive onto Pyramidal Neurons in the Infralimbic Prefrontal Cortex of Adult Rats | Nawreen N et al. | — | 2021 | — |
| Structural insights into GIRK2 channel modulation by cholesterol and PIP<sub>2</sub>. | Mathiharan YK et al. | — | 2021 | → |
| Therapeutic potential of targeting G protein-gated inwardly rectifying potassium (GIRK) channels in the central nervous system. | Jeremic D et al. | — | 2021 | → |
| A systematic review: Candidate gene and environment interaction on alcohol use and misuse among adolescents and young adults. | Kim J et al. | — | 2018 | → |
| Chronic Alcohol, Intrinsic Excitability, and Potassium Channels: Neuroadaptations and Drinking Behavior. | Cannady R et al. | — | 2018 | → |
| Genetics of Alcohol Use Disorder: A Role for Induced Pluripotent Stem Cells? | Prytkova I et al. | — | 2018 | → |
| Phosphoproteomic Analysis of the Amygdala Response to Adolescent Glucocorticoid Exposure Reveals G-Protein Coupled Receptor Kinase 2 as a Target for Reducing Motivation for Alcohol. | Bertholomey ML et al. | — | 2018 | → |
| A KCNJ6 gene polymorphism modulates theta oscillations during reward processing. | Kamarajan C et al. | — | 2017 | → |
| Differential potassium channel gene regulation in BXD mice reveals novel targets for pharmacogenetic therapies to reduce heavy alcohol drinking. | Rinker JA et al. | — | 2017 | → |
| Dual activation of neuronal G protein-gated inwardly rectifying potassium (GIRK) channels by cholesterol and alcohol. | Glaaser IW et al. | — | 2017 | → |
| Genes and Alcohol Consumption: Studies with Mutant Mice. | Mayfield J et al. | — | 2016 | → |
| Behavioral and Genetic Evidence for GIRK Channels in the CNS: Role in Physiology, Pathophysiology, and Drug Addiction. | Mayfield J et al. | — | 2015 | → |
| Endophenotypes for Alcohol Use Disorder: An Update on the Field. | Salvatore JE et al. | — | 2015 | → |
| Alcohol dependence: molecular and behavioral evidence. | Trudell JR et al. | — | 2014 | → |
| New insights into the therapeutic potential of Girk channels. | Luján R et al. | — | 2014 | → |
| Pharmacogenetics of addiction therapy. | Nielsen DA et al. | — | 2014 | → |
| Controversies about the enhanced vulnerability of the adolescent brain to develop addiction. | Bernheim A et al. | — | 2013 | → |
| Molecular basis of the facilitation of the heterooligomeric GIRK1/GIRK4 complex by cAMP dependent protein kinase. | Treiber F et al. | — | 2013 | → |
| Alcohol dependence as a chronic pain disorder. | Egli M et al. | — | 2012 | → |
| Family-based genome-wide association study of frontal θ oscillations identifies potassium channel gene KCNJ6. | Kang SJ et al. | — | 2012 | → |
| Genetic and environmental determinants of stress responding. | Clarke TK et al. | — | 2012 | → |
| The influence of gene-environment interactions on the development of alcoholism and drug dependence. | Enoch MA | — | 2012 | → |
| The contribution of imaging genetics to the development of predictive markers for addictions. | Loth E et al. | — | 2011 | → |