ArticleAlcoholism, clinical and experimental research2011
Haplotype-based study of the association of alcohol-metabolizing genes with alcohol dependence in four independent populations.
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 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Strong protective effect of the aldehyde dehydrogenase gene (ALDH2) 504lys (*2) allele against alcoholism and alcohol-induced medical diseases in Asians.Human genetics · 2012Pooled it
- Germline genetic variants in ABCB1, ABCC1 and ALDH1A1, and risk of hematological and gastrointestinal toxicities in a SWOG Phase III trial S0221 for breast cancer.The pharmacogenomics journal · 2014Trial
- Assessing the association between ADH5 and ALDH1A1 genetic variants and substance use disorder risk in a Jordanian male population.BMC genomics · 2025Article
- Relationship between moderate alcohol consumption, genetic polymorphisms and body weight in a population sample of Puerto Madryn, ArgentinaBiomedica : revista del Instituto Nacional de Salud · 2024Article
- Pharmacogenetic Profiling in High-Risk Soft Tissue Sarcomas Treated with Neoadjuvant Chemotherapy.Journal of personalized medicine · 2022Article
- GABA uptake transporters support dopamine release in dorsal striatum with maladaptive downregulation in a parkinsonism model.Nature communications · 2020Article
- Genome-wide association study of alcohol dependence in male Han Chinese and cross-ethnic polygenic risk score comparison.Translational psychiatry · 2019Article
- rs3764435 Associated With Parkinson's Disease in Mexican Mestizos: Case-Control Study Reveals Protective Effects Against Disease Development and Cognitive Impairment.Frontiers in neurology · 2019Article
- Association of CYP2C19*2 and ALDH1A1*1/*2 variants with disease outcome in breast cancer patients: results of a global screening array.European journal of clinical pharmacology · 2018Article
- Telomerase reverse transcriptase mutations in plasma DNA in patients with hepatocellular carcinoma or cirrhosis: Prevalence and risk factors.Hepatology communications · 2018Article
- Review: Genetic and environmental risk factors for alcohol use disorders in American Indians and Alaskan Natives.The American journal on addictions · 2017Review
- Genome-wide association study of body mass index in subjects with alcohol dependence.Addiction biology · 2017Article
- Parent and peer influences on emerging adult substance use disorder: A genetically informed study.Development and psychopathology · 2017Article
- Presynaptic Molecular Determinants of Quantal Size.Frontiers in synaptic neuroscience · 2016Review
- Aldehyde dehydrogenase 1a1 mediates a GABA synthesis pathway in midbrain dopaminergic neurons.Science (New York, N.Y.) · 2015Article
- Characterization of the metabolism of benzaldehyde dimethane sulfonate (NSC 281612, DMS612).Cancer chemotherapy and pharmacology · 2015Article
- Genetic influences on response to alcohol and response to pharmacotherapies for alcoholism.Pharmacology, biochemistry, and behavior · 2014Review
- Haplotype-based study of the association of alcohol and acetaldehyde-metabolising genes with alcohol dependence (with or without comorbid anxiety symptoms) in a Cape Mixed Ancestry population.Metabolic brain disease · 2014Article
- Rodent models of genetic contributions to motivation to abuse alcohol.Nebraska Symposium on Motivation. Nebraska Symposium on Motivation · 2014Review
- Allelic variants of ADH, ALDH and the five factor model of personality in alcohol dependence syndrome.Industrial psychiatry journal · 2014Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundEthanol is metabolized by 2 rate-limiting reactions: alcohol dehydrogenases (ADH) convert ethanol to acetaldehyde that is subsequently metabolized to acetate by aldehyde dehydrogenases (ALDH). Approximately 50% of East Asians have genetic variants that significantly impair this pathway and influence alcohol dependence (AD) vulnerability. We investigated whether variation in alcohol metabolism genes might alter the AD risk in four non-East Asian populations by performing systematic haplotype association analyses to maximize the chances of capturing functional variation.
methodsHaplotype-tagging SNPs were genotyped using the Illumina GoldenGate platform. Genotypes were available for 40 SNPs across the ADH genes cluster and 24 SNPs across the two ALDH genes in four diverse samples that included cases (lifetime AD) and controls (no Axis 1 disorders). The case control sample sizes were the following: Finnish Caucasians: 232, 194; African Americans: 267, 422; Plains American Indians: 226, 110; and Southwestern American (SW) Indians: 317, 72.
resultsIn all four populations, as well as HapMap populations, 5 haplotype blocks were identified across the ADH gene cluster: (i) ADH5-ADH4; (ii) ADH6-ADH1A-ADH1B; (iii) ADH1C; (iv) intergenic; (v) ADH7. The ALDH1A1 gene was defined by 4 blocks and ALDH2 by 1 block. No haplotype or SNP association results were significant after correction for multiple comparisons; however, several results, particularly for ALDH1A1 and ADH4, replicated earlier findings. There was an ALDH1A1 block 1 and 2 (extending from intron 5 to the 3' UTR) yin yang haplotype (haplotypes that have opposite allelic configuration) association with AD in the Finns driven by SNPs rs3764435 and rs2303317, respectively, and an ALDH1A1 block 3 (including the promoter region) yin yang haplotype association in SW Indians driven by 5 SNPs, all in allelic identity. The ADH4 SNP rs3762894 was associated with AD in Plains Indians.
conclusionsThe systematic evaluation of alcohol-metabolizing genes in four non-East Asian populations has shown only modest associations with AD, largely for ALDH1A1 and ADH4. A concentration of signals for AD with ALDH1A1 yin yang haplotypes in several populations warrants further study.
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