Three μ-opioid receptor gene (OPRM1) variants and two κ-opioid receptor gene (OPRK1) variants were examined in 314 male patients with AUD and 324 male controls.
All three variants were associated with AUD across allelic and genotypic models: ALDH2, ORs = 0.25, P < 0.001; ADH1B, ORs = 0.22-0.49, P < 0.001; ADH1C, ORs = 0.26-0.46, P < 0.001.
This single molecule localization microscopy technique was employed to quantitatively characterize the effects of pharmacologically relevant concentrations of ethanol and naltrexone (an opioid receptor antagonist and medication used to treat alcohol use disorders) on the lateral nano-organization of mu and kappa opioid receptors (MOR and KOR, respectively).
We characterized the effects of the mu opioid peptide (MOP) receptor agonist buprenorphine and the buprenorphine analog (2S)-2-[(5R,6R,7R,14S)-N-cyclopropylmethyl-4,5-epoxy-6,14-ethano-3-hydroxy-6 methoxymorphinan-7-yl]-3,3-dimethylpentan-2-ol (BU08028), which stimulates MOP and NOP receptors, in a translational nonhuman primate model of AUD.
The present study suggests that both rare and common variant associations in GABRA2 confer risk for alcohol use disorder and antisocial behaviors, indicating a potential liability toward externalizing behavior more broadly.
Differences in intervention effects by GABRA2 genotype were most pronounced from ages 13 to 16-a period when drinking is associated with increased risk for alcohol use disorder.
Use of aldehyde-induced adducts to monitor AUD may also be important when considering that approximately 540 million people bear a genetic variant of aldehyde dehydrogenase 2 (ALDH2) predisposing this population to aldehyde-induced toxicity with alcohol use.
Some studies show that AUD patients carrying the G-allele of the OPRM1 variant c.118A>G respond better to naltrexone, resulting in reduced relapse rates compared to carriers of the AA genotype.
GABRA2-a known genetic marker for alcohol use disorder and epilepsy-significantly affected beta power, consistent with the known relation between GABA<sub>A</sub> interneuron activity and beta oscillations.
With longitudinal EHR data from the Million Veteran Program (MVP) linked to genetic data, we used two population-specific polymorphisms in ADH1B that are associated strongly with AUD in African Americans (AAs) and European Americans (EAs): rs2066702 (Arg369Cys, AAs) and rs1229984 (rs1229984" genes_norm="125">Arg48His, EAs) as criterion measures.
Specifically, the ADH1B*3 allele is present almost exclusively in Black populations and has been protective against alcohol use and alcohol use disorder.
For the BAES stimulation subscale scores, adjusting for age, baseline scores, and time effects, individuals with 2 copies of the GABRA2rs279858 C "risk" allele for AUD exhibited the greatest stimulant responses to high-dose alcohol compared to the other risk allele counts (dose-by-allele count interaction effect, p = 0.001, post hoc contrast for C-allele, p = 0.012).
However, the suppressive effects of inactive ALDH2 and highly active ADH1B for AUDs are only partial and interact with other factors, such as personality traits, psychiatric comorbidities, and environmental factors.
The purpose of the present study was to examine the effects of GABRA2 genotype and stressful life events on aggressive behaviour, alcohol use frequency and occurrence of alcohol use disorder in a population representative sample of adolescents followed up from third grade to 25 years of age.
We evaluated the presence of SNPs in the ADH (ADH1B, ADH1C, and ADH4) and ALDH (ALDH2) genes in alcohol users of Goiânia, State of Goiás - Brazil, and then we established a possible relationship with AUD by allelic and genotypic study.
Being Chinese and possessing an ALDH2*2 allele within Koreans both buffered against the risk for AUD symptoms associated with earlier ADI, indicating that this relationship can be attenuated by protective factors.
However, the suppressive effects of inactive ALDH2 and highly active ADH1B for AUDs are only partial and interact with other factors, such as personality traits, psychiatric comorbidities, and environmental factors.
Therefore, among those at risk for greater consumption, e.g. those who experienced childhood adversity, ADH1B-rs1229984 appears to have a stronger effect on alcohol consumption and consequently on risk for AUD symptom severity.