rs671

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Geno	Mag	Summary
(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.

Reference

GRCh38 38.1/141

Chromosome

12

Position

111803962

Gene

ALDH2

is a	snp
is	mentioned by
dbSNP	rs671
dbSNP (classic)	rs671
ClinGen	rs671
ebi	rs671
HLI	rs671
Exac	rs671
Gnomad	rs671
Varsome	rs671
LitVar	rs671
Map	rs671
PheGenI	rs671
Biobank	rs671
1000 genomes	rs671
hgdp	rs671
ensembl	rs671
geneview	rs671
scholar	rs671
google	rs671
pharmgkb	rs671
gwascentral	rs671
openSNP	rs671
23andMe	rs671
SNPshot	rs671
SNPdbe	rs671
MSV3d	rs671
GWAS Ctlg	rs671

GMAF

0.05739

Max Magnitude

4

?

(A;A) (A;G) (G;G)

28

rs671 is a classic SNP, well known in a sense through the phenomena known as the "alcohol flush", also known as the "Asian Flush" or "Asian blush", in which certain individuals, often of Asian descent, have their face, neck and sometimes shoulders turn red after drinking alcohol.[PMID 6582480 ]

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]

Disulfiram (Antabuse) is probably an ineffective treatment for alcohol dependence in people who have the Asian Flush.

Tests for the alcohol flush reaction at deCODEme are based on rs671.

23andMe blog carriers of the A allele are prone to esophageal cancer, which is also known as upper aerodigestive tract (UAT) cancer, due to acetaldehyde from smoking.

OMIM	100650
Desc	ALCOHOL SENSITIVITY, ACUTE
Variant	0001
Related	also

[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

GWAS snp
PMID	[PMID 20139978]
Trait	Hematological and biochemical traits
Title	Genome-wide association study of hematological and biochemical traits in a Japanese population
Risk Allele	A
P-val	7E-10
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

GWAS snp
PMID	[PMID 22171074]
Trait
Title	A genome-wide association and gene-environment interaction study for serum triglycerides levels in a healthy Chinese male population.
Risk Allele
P-val	0.000002
Odds Ratio	None None

GWAS snp
PMID	[PMID 21971053 ]
Trait
Title	Genome-wide association study of coronary artery disease in the Japanese.
Risk Allele	A
P-val	2E-34
Odds Ratio	1.4300 [1.35-1.51]

GWAS snp
PMID	[PMID 22286173]
Trait
Title	Genome-wide association study for intracranial aneurysm in the Japanese population identifies three candidate susceptible loci and a functional genetic variant at EDNRA.
Risk Allele	C
P-val	0.000003
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

ClinVar
Risk	Rs671(A;A)
Alt	Rs671(A;A)
Reference	Rs671(G;G)
Significance	Other
Disease	Acute alcohol sensitivity Alcohol dependence Susceptibility to hangover Sublingual nitroglycerin Esophageal cancer
Variation	info
Gene	ALDH2
CLNDBN	Acute alcohol sensitivity Alcohol dependence Susceptibility to hangover Sublingual nitroglycerin, susceptibility to poor response to Esophageal cancer, alcohol-related, susceptibility to
Reversed	0
HGVS	NC_000012.11:g.112241766G>A
CLNSRC	OMIM Allelic Variant UniProtKB (protein)
CLNACC	RCV000020058.2, RCV000020059.2, RCV000020060.2, RCV000020061.2, RCV000020062.2,

[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

Alcohol Consumption, Smoking and Risk of Esophageal Cancer

GWAS snp
PMID	[PMID 22797727 ]
Trait	Renal function-related traits (sCR)
Title	Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations.
Risk Allele	A
P-val	3E-10
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

GWAS snp
PMID	[PMID 24861553 ]
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.
Risk Allele	G
P-val	3E-11
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

[PMID 25636114] [Advance in research on the association of ALDH2 gene polymorphisms with cancer susceptibility in drinkers]

[PMID 26842247] Association Study of Gene Polymorphisms in GABA, Serotonin, Dopamine, and Alcohol Metabolism Pathways with Alcohol Dependence in Taiwanese Han Men.

[PMID 27643160] APSH YI-02 THE POLYMORPHISM IN ALDEHYDE DEHYDROGENASE-2 (ALDH2) GENE IS ASSOCIATED WITH MYOCARDIAL INFARCTION AND STROKE IN A CHINESE POPULATION.

[PMID 27754203] APSH YI-02 THE POLYMORPHISM IN ALDEHYDE DEHYDROGENASE-2 (ALDH2) GENE IS ASSOCIATED WITH MYOCARDIAL INFARCTION AND STROKE IN A CHINESE POPULATION.

[PMID 28348376 ] A missense single nucleotide polymorphism in the ALDH2 gene, rs671, is associated with hip fracture.

[PMID 28485404 ] Genetic contributors to variation in alcohol consumption vary by race/ethnicity in a large multi-ethnic genome-wide association study.

[PMID 28594837 ] Genetic variants in ALDH1B1 and alcohol dependence risk in a British and Irish population: A bioinformatic and genetic study.

[PMID 28613083] The ALDH2 gene rs671 polymorphism is not associated with essential hypertension.

[PMID 29408531] The polymorphism rs671 at ALDH2 associated with serum uric acid levels in Chinese Han males: A genome-wide association study.

[PMID 29460428 ] Genomewide association study of alcohol dependence and related traits in a Thai population.

[PMID 29722023] Discovery of four exonic and one intergenic novel susceptibility loci for leprosy.

[PMID 30507608 ] Not just correlative: a new pathway defines how an ALDH2 SNP contributes to atherosclerosis.

[PMID 30639619] Alcohol Intake Interacts with Functional Genetic Polymorphisms of Aldehyde Dehydrogenases (ALDH2) and Alcohol Dehydrogenase (ADH) to Increase Esophageal Squamous Cell Cancer Risk.

[PMID 31338989] Causal effect of alcohol consumption on hyperuricemia using a Mendelian randomization design.

[PMID 31366848] [Development of Novel Genotyping Protocol and Its Application for Genotyping of Alcohol Metabolism-related Genes].

[PMID 31591379 ] Genome-wide association study of alcohol dependence in male Han Chinese and cross-ethnic polygenic risk score comparison.

[PMID 30375985 ] Acetaldehyde dehydrogenase 2 interactions with LDLR and AMPK regulate foam cell formation.

[PMID 32896553] A critical assessment of the potential of pharmacological modulation of aldehyde dehydrogenases to treat the diseases of bone loss.

[PMID 33188956] ALDH2 mutation promotes skeletal muscle atrophy in mice via accumulation of oxidative stress.