Altered Gamma-Aminobutyric Acid Type B Receptor Subunit 1 Splicing In Alcoholics

Lee, Changhoon; Mayfield, R. Dayne; Harris, R. Adron

doi:10.1016/j.biopsych.2013.08.028

Cited by 28 publications

(24 citation statements)

References 44 publications

(62 reference statements)

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“…For example, alcohol affects pre-mRNA alternative splicing at DRD2 which encodes the dopamine type 2 receptor (Wernicke et al, 2010), NMDA receptor NR1 subunit encoded by GRIN1 that can produce as many as eight spliced variants (Hardy et al, 1999; Honse et al, 2003; Kumari, 2001), and BK channel alpha1 subunit (Pietrzykowski et al, 2008). In addition, altered GABA-B receptor subunit 1 splicing is observed in human alcoholic post-mortem brain (Lee et al, 2014). Thus it can be reasonably hypothesized that genetic variation in MBNL2 may affect alcohol dependence phenotypes by altering alternative splicing mechanisms that are known to contribute to splicing of alcohol-responsive proteins.…”

Section: Genome-wide Association Studies Of Alcohol Dependencementioning

confidence: 99%

Genetic studies of alcohol dependence in the context of the addiction cycle

et al. 2017

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Family, twin and adoption studies demonstrate clearly that alcohol dependence and alcohol use disorders are phenotypically complex and heritable. The heritability of alcohol use disorders is estimated at approximately 50–60% of the total phenotypic variability. Vulnerability to alcohol use disorders can be due to multiple genetic or environmental factors or their interaction which gives rise to extensive and daunting heterogeneity. This heterogeneity makes it a significant challenge in mapping and identifying the specific genes that influence alcohol use disorders. Genetic linkage and (candidate gene) association studies have been used now for decades to map and characterize genomic loci and genes that underlie the genetic vulnerability to alcohol use disorders. These approaches have been moderately successful in identifying several genes that contribute to the complexity of alcohol use disorders. Recently, genome-wide association studies have become one of the major tools for identifying genes for alcohol use disorders by examining correlations between millions of common single-nucleotide polymorphisms with diagnosis status. Genome-wide association studies are just beginning to uncover novel biology; however, the functional significance of results remains a matter of extensive debate and uncertainty. In this review, we present a select group of genome-wide association studies of alcohol dependence, as one example of a way to generate functional hypotheses, within the addiction cycle framework. This analysis may provide novel directions for validating the functional significance of alcohol dependence candidate genes. This article is part of the Special Issue entitled “Alcoholism”.

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Section: Genome-wide Association Studies Of Alcohol Dependencementioning

confidence: 99%

Genetic studies of alcohol dependence in the context of the addiction cycle

et al. 2017

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“…Drugs of abuse such as alcohol can affect alternative splicing. For example, chronic alcohol consumption enhances the complexity of GABA(B) receptor splicing (Lee et al, 2010, 2013). Human alcoholics show differences in GABA(B) receptor splice variants when compared to non-alcoholics, which may contribute to the pharmacologic effects of GABA(B) agonists such as baclofen in the treatment of alcoholism (Lee et al, 2013).…”

Section: Molecular Mechanisms Underlying Acute and Chronic Alcoholismmentioning

confidence: 99%

Molecular basis of alcoholism

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Ferguson

Harris

2014

Handbook of Clinical Neurology

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“…Chronic alcohol abuse leads to aberrant splicing of the GABA B ligand-binding subunit (GABA B1 ) in the prefrontal cortex [35], which is postulated to reduce GABA B receptor function in response to ligand, increasing the dose of agonist required in the clinic for effective treatment. It is unknown whether the splicing of GABA B receptor is altered in other painful neuropathies.…”

Section: Gpcrs Alternative Splice Variants and Painmentioning

confidence: 99%