ArticleAlcoholism, clinical and experimental research2011
Variation in genes encoding the neuroactive steroid synthetic enzymes 5α-reductase type 1 and 3α-reductase type 2 is associated with alcohol dependence.
Article in Alcoholism, clinical and experimental research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 37 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
- Variation in AKR1C3, which encodes the neuroactive steroid synthetic enzyme 3α-HSD type 2 (17β-HSD type 5), moderates the subjective effects of alcohol.Psychopharmacology · 2014Trial
- Steroid 5α-reductases in the brain: From neurosteroidogenesis to therapeutic implications.Frontiers in neuroendocrinology · 2026Review
- Allopregnanolone: An overview on its synthesis and effects.Journal of neuroendocrinology · 2022Review
- Basic Human Body Dimensions Relate to Alcohol Dependence and Predict Hospital Readmission.Journal of clinical medicine · 2019Article
- Dynamic Adaptation in Neurosteroid Networks in Response to Alcohol.Handbook of experimental pharmacology · 2018Article
- Ethanol withdrawal-induced dysregulation of neurosteroid levels in plasma, cortex, and hippocampus in genetic animal models of high and low withdrawal.Psychopharmacology · 2017Article
- Article
- Alcohol Effects on Stress Pathways: Impact on Craving and Relapse Risk.Canadian journal of psychiatry. Revue canadienne de psychiatrie · 2016Review
- Neurosteroidogenesis Today: Novel Targets for Neuroactive Steroid Synthesis and Action and Their Relevance for Translational Research.Journal of neuroendocrinology · 2016Review
- Null mutation of 5α-reductase type I gene alters ethanol consumption patterns in a sex-dependent manner.Behavior genetics · 2015Article
- The pharmacogenetics of alcohol use disorder.Alcoholism, clinical and experimental research · 2015Review
- Divergent neuroactive steroid responses to stress and ethanol in rat and mouse strains: relevance for human studies.Psychopharmacology · 2014Review
- Association of V89L SRD5A2 polymorphism with craving and serum leptin levels in male alcohol addicts.Psychopharmacology · 2012Article
- Article
- Localization of brain 5α-reductase messenger RNA in mice selectively bred for high chronic alcohol withdrawal severity.Alcohol (Fayetteville, N.Y.) · 2011Article
- Alcohol exposure during late adolescence increases drinking in adult Wistar rats, an effect that is not reduced by finasteride.Alcohol and alcoholism (Oxford, Oxfordshire)Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundStudies of alcohol effects in rodents and in vitro implicate endogenous neuroactive steroids as key mediators of alcohol effects at GABA(A) receptors. We used a case-control sample to test the association with alcohol dependence (AD) of single nucleotide polymorphisms in the genes encoding two key enzymes required for the generation of endogenous neuroactive steroids: 5α-reductase, type I (5α-R), and 3α-hydroxysteroid dehydrogenase, type 2 (3α-HSD), both of which are expressed in human brain.
methodsWe focused on markers previously associated with a biological phenotype. For 5α-R, we examined the synonymous SRD5A1 exon 1 SNP rs248793, which has been associated with the ratio of dihydrotestosterone to testosterone. For 3α-HSD, we examined the nonsynonymous AKR1C3 SNP rs12529 (H5Q), which has been associated with bladder cancer. The SNPs were genotyped in a sample of 1,083 non-Hispanic Caucasians including 552 controls and 531 subjects with AD.
resultsThe minor allele for both SNPs was more common among controls than subjects with AD: SRD5A1 rs248793 C-allele (χ(2)(1) = 7.6, p = 0.006) and AKR1C3 rs12529 G-allele (χ(2)(1) = 14.6, p = 0.0001). There was also an interaction of these alleles such that the "protective" effect of the minor allele at each marker for AD was conditional on the genotype of the second marker.
conclusionsWe found evidence of an association with AD of polymorphisms in two genes encoding neuroactive steroid biosynthetic enzymes, providing indirect evidence that neuroactive steroids are important mediators of alcohol effects in humans.
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