|(A;A)||4||Asian Flusher; increased risk of esophageal cancer; East Asian ancestry; Disulfiram not effective for alcoholism.|
|(A;G)||3.5||Asian Flush; worse hangovers; increased risk of esophageal cancer; East Asian ancestry; Disulfiram probably not effective for alcoholism.|
|(G;G)||2||Alcohol Flush: Normal, doesn't flush. Normal hangovers. Normal risk of Alcoholism. Normal risk of Esophageal Cancer. Disulfiram is effective for alcoholism.|
The rs671(A) allele of the ALDH2 gene is the culprit, in that it encodes a form of the aldehyde dehydrogenase 2 protein that is defective at metabolizing alcohol. This allele is known as the ALDH*2 form, and individuals possessing either one or two copies of it show alcohol-related sensitivity responses including facial flushing, and severe hangovers (and hence they are usually not regular drinkers). Perhaps not surprisingly they appear to suffer less from alcoholism and alcohol-related liver disease. [PMID 511165, PMID 16046871]
Tests for the alcohol flush reaction at deCODEme are based on rs671.
[PMID 19698717] Functional variants in ADH1B and ALDH2 coupled with alcohol and smoking synergistically enhance esophageal cancer risk
[PMID 19706845] A Novel Polymorphism rs1329149 of CYP2E1 and a Known Polymorphism rs671 of ALDH2 of Alcohol Metabolizing Enzymes Are Associated with Colorectal Cancer in a Southwestern Chinese Population
[PMID 20093384] Impact of smoking on lung cancer risk is stronger in those with the homozygous aldehyde dehydrogenase 2 (ALDH2) null allele in a Japanese population
[PMID 19641380] Candidate gene polymorphisms for diabetes mellitus, cardiovascular disease and cancer are associated with longevity in Koreans
|Trait||Hematological and biochemical traits|
|Title||Genome-wide association study of hematological and biochemical traits in a Japanese population|
|Odds Ratio||0.26 [NR] % variance|
[PMID 20833657] Strong interaction between the effects of alcohol consumption and smoking on oesophageal squamous cell carcinoma among individuals with ADH1B and/or ALDH2 risk alleles
[PMID 21372407] Confirmation of ALDH2 as a Major Locus of Drinking Behavior and of Its Variants Regulating Multiple Metabolic Phenotypes in a Japanese Population
[PMID 21476199] Acetaldehyde dehydrogenase 2 SNP rs671 and susceptibility to essential hypertension in Mongolians: a case control study
[PMID 22102315] Strong protective effect of the aldehyde dehydrogenase gene (ALDH2) 504lys (*2) allele against alcoholism and alcohol-induced medical diseases in Asians
|Title||A genome-wide association and gene-environment interaction study for serum triglycerides levels in a healthy Chinese male population.|
|Odds Ratio||None None|
|Title||Genome-wide association study of coronary artery disease in the Japanese.|
|Odds Ratio||1.4300 [1.35-1.51]|
|Title||Genome-wide association study for intracranial aneurysm in the Japanese population identifies three candidate susceptible loci and a functional genetic variant at EDNRA.|
|Odds Ratio||1.2400 None|
[PMID 22508505] Aldehyde-stress resulting from Aldh2 mutation promotes osteoporosis due to impaired osteoblastogenesis
[PMID 22551939] Association of a functional single-nucleotide polymorphism in the ALDH2 gene with essential hypertension depends on drinking behavior in a Chinese Han population
|Disease||Acute alcohol sensitivity Alcohol dependence Susceptibility to hangover Sublingual nitroglycerin ESOPHAGEAL CANCER|
|CLNDBN||Acute alcohol sensitivity Alcohol dependence Susceptibility to hangover Sublingual nitroglycerin, susceptibility to poor response to ESOPHAGEAL CANCER, ALCOHOL-RELATED, SUSCEPTIBILITY TO|
|CLNSRC||ClinVar OMIM Allelic Variant|
|CLNACC||RCV000020058.1, RCV000020059.1, RCV000020060.1, RCV000020061.1, RCV000020062.1,|
[PMID 18317873] Statistical analysis of the associations between polymorphisms within aldehyde dehydrogenase 2 (ALDH2), and quantitative and qualitative traits extracted from a large-scale database of Japanese single-nucleotide polymorphisms (SNPs).
[PMID 18331377] Association of ADH and ALDH genes with alcohol dependence in the Irish Affected Sib Pair Study of alcohol dependence (IASPSAD) sample.
[PMID 18996923] Associations of ADH and ALDH2 gene variation with self report alcohol reactions, consumption and dependence: an integrated analysis.
[PMID 19041386] Genetic-epidemiological evidence on genes associated with HDL cholesterol levels: a systematic in-depth review.
[PMID 19262484] Gene-environmental interaction regarding alcohol-metabolizing enzymes in the Japanese general population.
[PMID 20417517] The ALDH2 Glu504Lys polymorphism is associated with coronary artery disease in Han Chinese: Relation with endothelial ADMA levels.
[PMID 20518787] Comparison between self-reported facial flushing after alcohol consumption and ALDH2 Glu504Lys polymorphism for risk of upper aerodigestive tract cancer in a Japanese population.
[PMID 20616999] Usefulness of Mendelian randomization in observational epidemiology.
[PMID 21351086] Shortened telomeres in individuals with abuse in alcohol consumption.
[PMID 21437268] A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium.
[PMID 21455501] Genetic variants on chromosome 8q24 and colorectal neoplasia risk: a case-control study in China and a meta-analysis of the published literature.
[PMID 21576033] ADH1B and ALDH2 polymorphisms and their associations with increased risk of squamous cell carcinoma of the head and neck in the Korean population.
[PMID 21900886] Pharmacogenetics of naltrexone in asian americans: a randomized placebo-controlled laboratory study.
[PMID 21917409] Alcohol drinking, mean corpuscular volume of erythrocytes, and alcohol metabolic genotypes in drunk drivers.
[PMID 21946912] Folate, alcohol, and aldehyde dehydrogenase 2 polymorphism and the risk of oral and pharyngeal cancer in Japanese.
[PMID 22004425] Genetic risk of hepatocellular carcinoma in patients with hepatitis C virus: a case control study.
[PMID 23060937] A variant allele of ADH1B and ALDH2, is associated with the risk of esophageal cancer
|qualified_impact||Insufficiently evaluated pathogenic|
|Trait||Renal function-related traits (sCR)|
|Title||Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations.|
|Odds Ratio||.00 [0.0031-0.0059] mg/dl increase|
[PMID 23685282] Association of genetic polymorphisms in ADH and ALDH2 with risk of coronary artery disease and myocardial infarction: A meta-analysis
[PMID 23697560] ALDH2 rs671 Polymorphism and Coronary Heart Disease Risk Among Asian Populations: A Meta-Analysis and Meta-Regression
[PMID 23430454] Genetic variants at 4q21, 4q23 and 12q24 are associated with esophageal squamous cell carcinoma risk in a Chinese population
[PMID 24277619] Associated to alcohol dependence and is the major genetic determinant of "daily maximum drinks" in a GWAS study of an isolated rural Chinese sample
[PMID 22560290] A comparison of Val81Met and other polymorphisms of alcohol metabolising genes in patients and controls in Northern Spain.
[PMID 22930414] Single nucleotide polymorphisms of ADH1B, ADH1C and ALDH2 genes and esophageal cancer: a population-based case-control study in China.
[PMID 23088731] Tag single nucleotide polymorphisms of alcohol-metabolizing enzymes modify the risk of upper aerodigestive tract cancers: HapMap database analysis.
[PMID 23243119] Is aldehyde dehydrogenase 2 a credible genetic instrument for alcohol use in Mendelian randomization analysis in Southern Chinese men?
[PMID 23364009] Common variants at 12q24 are associated with drinking behavior in Han Chinese.
[PMID 23455379] The aldehyde dehydrogenase 2 (ALDH2) Glu504Lys polymorphism interacts with alcohol drinking in the risk of stomach cancer.
[PMID 25427900] Genetic-Epidemiological Evidence for the Role of Acetaldehyde in Cancers Related to Alcohol Drinking
|Trait||Body mass index|
|Title||Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index.|
|Odds Ratio||.04 [0.027-0.049] unit increase|
[PMID 25680115] Association between Glu504Lys Polymorphism of ALDH2 Gene and Cancer Risk: A Meta-Analysis
[PMID 25848305] Clinical significance of ALDH2 rs671 polymorphism in esophageal cancer: evidence from 31 case-control studies
[PMID 25102261] Maternal folate, alcohol and energy metabolism-related gene polymorphisms and the risk of recurrent pregnancy loss
[PMID 25524923] Genetic polymorphisms of ADH1B, ADH1C and ALDH2, alcohol consumption, and the risk of gastric cancer: the Japan Public Health Center-based prospective study