Trial reportPsychopharmacology2014
Variation in AKR1C3, which encodes the neuroactive steroid synthetic enzyme 3α-HSD type 2 (17β-HSD type 5), moderates the subjective effects of alcohol.
Trial report in Psychopharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
10 citing papers in PubMed, 14 citations in OpenAlex.
- Pregnenolone effects on provoked alcohol craving, anxiety, HPA axis, and autonomic arousal in individuals with alcohol use disorder.Psychopharmacology · 2023Trial
- Neuroactive steroid levels and cocaine use chronicity in men and women with cocaine use disorder receiving progesterone or placebo.The American journal on addictions · 2019Trial
- Effects of progesterone stimulated allopregnanolone on craving and stress response in cocaine dependent men and women.Psychoneuroendocrinology · 2016Trial
- Induced pluripotent stem cell reprogramming-associated methylation at the GABRA2 promoter and chr4p12 GABAAmerican journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2020Article
- Molecular Correlates of Topiramate and GRIK1 rs2832407 Genotype in Pluripotent Stem Cell-Derived Neural Cultures.Alcoholism, clinical and experimental research · 2020Article
- Alcohol-responsive genes identified in human iPSC-derived neural cultures.Translational psychiatry · 2019Article
- Examining the effects of alcohol on GABAAlcohol (Fayetteville, N.Y.) · 2018Article
- Examining FKBP5 mRNA expression in human iPSC-derived neural cells.Psychiatry research · 2017Article
- GABRA2 Alcohol Dependence Risk Allele is Associated with Reduced Expression of Chromosome 4p12 GABAA Subunit Genes in Human Neural Cultures.Alcoholism, clinical and experimental research · 2015Article
- The pharmacogenetics of alcohol use disorder.Alcoholism, clinical and experimental research · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
rationaleAnimal models suggest that neuroactive steroids contribute to alcohol's acute effects. We previously reported that a common nonsynonymous polymorphism, AKR1C3 2 in the gene encoding the enzyme 3α-HSD2/17β-HSD5, and a synonymous single nucleotide polymorphism (SNP), rs248793, in SRD5A1, which encodes 5α-reductase, were associated with alcohol dependence (AD).
objectivesThe aim of the study was to investigate whether these polymorphisms moderate subjective effects of alcohol in humans and whether AKR1C3 2 affects neuroactive steroid synthesis.
methodsSixty-five Caucasian men (34 lighter and 31 heavier drinkers; mean age 26.2 years) participated in a double-blind laboratory study where they consumed drinks containing no ethanol or 0.8 g/kg of ethanol. Breath alcohol, heart rate (HR), and self-reported alcohol effects were measured at 40-min intervals, and genotype was examined as a moderator of alcohol's effects. Levels of the neuroactive steroid 5α-androstane-3α,17β-diol and its precursors, 3α,5α-androsterone and dihydrotestosterone, were measured at study entry using GC/MS.
resultsInitially, carriers of the AD-protective AKR1C3 2 G allele had higher levels of 5α-androstane-3α,17β-diol relative to the precursor 3α,5α-androsterone than C allele homozygotes. AKR1C3 2 G allele carriers exhibited greater increases in heart rate and stimulant and sedative effects of alcohol than C allele homozygotes. The genotype effects on sedation were observed only in heavier drinkers. The only effect of the SRD5A1 SNP was to moderate HR. There were no interactive effects of the two SNPs.
conclusionsThe observed effects of variation in a gene encoding a neuroactive steroid biosynthetic enzyme on the rate of 17β-reduction of androsterone relative to androstanediol and on alcohol's sedative effects may help to explain the association of AKR1C3 2 with AD.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.