Rs671

Orientation

plus

is a	snp
is	mentioned by
dbSNP	rs671
PheGenI	rs671
nextbio	rs671
hapmap	rs671
1000 genomes	rs671
hgdp	rs671
ensembl	rs671
gopubmed	rs671
geneview	rs671
scholar	rs671
google	rs671
pharmgkb	rs671
gwascentral	rs671
openSNP	rs671
23andMe	rs671
23andMe all	rs671
SNP Nexus
SNPshot	rs671
SNPdbe	rs671
MSV3d	rs671

Gene

ALDH2

Chromosome

12

Orientation

plus

Position

112241766

Reference

GRCh37 37.1/131

Max Magnitude

4

Geno	Mag	Summary
(A;A)	4	Flusher, increased risk of esophageal cancer
(A;G)	3.5	experiences asian flush
(G;G)	0	normal

?	(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]

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.

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)
Normal	rs671(G;G)
Significance	255
Disease	Alcohol dependence
ClinVar	info
Gene	ALDH2
CLNDBN	Alcohol dependence
Reversed	0
CLNHGVS	NC_000012.11:g.112241766G>A
CLNSRC	OMIM Allelic Variant

[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

GET Evidence
ALDH2-E504K
aa_change	Glu504Lys
aa_change_short	E504K
impact	pathogenic
qualified_impact	Insufficiently evaluated pathogenic
overall_frequency	0.0104167
summary

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