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rs1229984

From SNPedia

Orientationminus
Stabilizedminus
Geno Mag Summary
(A;A) 2 0.56x decreased risk of oral/throat cancers
(A;G) 2 0.56x decreased risk of oral/throat cancers
(G;G) 1.1 normal oral/throat cancer risk; more frequent alcohol consumption
ReferenceGRCh38 38.1/141
Chromosome4
Position99318162
GeneADH1B
is asnp
is mentioned by
dbSNPrs1229984
ebirs1229984
HLIrs1229984
Exacrs1229984
Varsomers1229984
Maprs1229984
PheGenIrs1229984
hapmaprs1229984
1000 genomesrs1229984
hgdprs1229984
ensemblrs1229984
gopubmedrs1229984
geneviewrs1229984
scholarrs1229984
googlers1229984
pharmgkbrs1229984
gwascentralrs1229984
openSNPrs1229984
23andMers1229984
23andMe allrs1229984
SNP Nexus

SNPshotrs1229984
SNPdbers1229984
MSV3drs1229984
GWAS Ctlgrs1229984
Merged fromRs17856968
GMAF0.2117
Max Magnitude2
? (A;A) (A;G) (G;G) 28
A SNP in rs1229984 encodes a form of the alcohol dehydrogenase ADH1B gene that significantly reduces the clearance rate of alcohol from the liver. This SNP is also known as Arg48His, with the (G) allele corresponding to the Arg and the (A) to the His.

Known in the literature as ADH2*2 or sometimes ADH1B*2, the allele with increased activity (meaning more rapid oxidation of ethanol to acetaldehyde) is His48, encoded by rs1229984(A). Individuals with one or especially two ADH2*2 alleles, ie genotypes rs1229984(A;G) or rs1229984(A;A) are more likely to find drinking unpleasant and have a somewhat reduced risk for alcoholism. [PMID 7635462] [PMID 21968928OA-icon.png]

A study of over 3,800 cases of "upper aerodigestive" cancers (mouth/throat, voice box, and esophageal cancers) concluded that the rs1229984(A) allele (in dbSNP orientation) has a protective effect. Carriers of this allele had a 0.56x (decreased; p=10-10) risk of having one of these cancer types.[PMID 18500343]

A review of the (at times conflicting) findings regarding ADH1B genotypes and maternal and fetal alcohol syndromes is available.[1]

A study of 4,500+ Australian twins concluded that rs1229984(G) carriers flush less after alcohol consumption, consumed alcohol on more occasions, had a higher maximum number of alcoholic drinks in a single day and had a higher overall alcohol consumption in the previous year than those with the less common (A) allele. [PMID 18996923OA-icon.png]

The rs1229984(A;G) genotype might be associated with a decreased risk for migraine, and the rs1229984(A) allele may be related with the risk for triggering migraine attacks after alcohol consumption based on a study of 197 Spanish patients.[PMID 19486361]

Note: this is not the SNP associated with the "Asian Blush" (rs671), although there are several studies looking at individuals with varying combinations of SNPs rs671 and rs1229984.

OMIM103720
DescALCOHOL DEHYDROGENASE, BETA SUBUNIT, 'TYPICAL'/'ATYPICAL'
Variant0001
Relatedalso
[PMID 19298322OA-icon.png] Associations and Interactions Between SNPs in the Alcohol Metabolizing Genes and Alcoholism Phenotypes in European Americans.

According to a 23andMe discussion This is one of the SNPs which were re-analyzed April 2009. Customers with older data may wish to redownload. SNPs effected rs4420638, rs34276300, rs3091244, rs34601266, rs2033003, rs7900194, rs9332239, rs28371685, rs1229984, and rs28399504.


[PMID 19687126OA-icon.png] A non-synonymous variant in ADH1B is strongly associated with prenatal alcohol use in a European sample of pregnant women

[PMID 19698717] Functional variants in ADH1B and ALDH2 coupled with alcohol and smoking synergistically enhance esophageal cancer risk



[PMID 19861527] Impact of multiple alcohol dehydrogenase gene polymorphisms on risk of upper aerodigestive tract cancers in a Japanese population


[PMID 20205700] Genetic determinants of both ethanol and acetaldehyde metabolism influence alcohol hypersensitivity and drinking behaviour among Scandinavians


[PMID 20158305] Associations between ADH gene variants and alcohol phenotypes in Dutch adults

[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 21437268OA-icon.png] A Genome-Wide Association Study of Upper Aerodigestive Tract Cancers Conducted within the INHANCE Consortium


[PMID 22144473] Genetic variation in alcohol dehydrogenase (ADH1A, ADH1B, ADH1C, ADH7) and aldehyde dehydrogenase (ALDH2), alcohol consumption, and gastric cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort


[PMID 21940907OA-icon.png] Joint effects of alcohol consumption and polymorphisms in alcohol and oxidative stress metabolism genes on risk of head and neck cancer


[PMID 22690706] Association of alcohol dehydrogenase polymorphisms and lifestyle factors with excessive alcohol intake within the Spanish population (EPIC-Spain)


ClinVar
Risk rs1229984(G;G)
Alt rs1229984(G;G)
Reference rs1229984(A;A)
Significance Other
Disease Alcohol dependence Aerodigestive tract cancer
Variation info
Gene ADH1B
CLNDBN Alcohol dependence Aerodigestive tract cancer, squamous cell, alcohol-related, protection against
Reversed 1
HGVS NC_000004.11:g.100239319T\x3d
CLNSRC OMIM Allelic Variant
CLNACC RCV000019813.2, RCV000019814.3,



[PMID 12050823OA-icon.png] A global perspective on genetic variation at the ADH genes reveals unusual patterns of linkage disequilibrium and diversity.

[PMID 16255080OA-icon.png] A haplotype map of the human genome.

[PMID 16685648OA-icon.png] Diplotype trend regression analysis of the ADH gene cluster and the ALDH2 gene: multiple significant associations with alcohol dependence.

[PMID 17185388OA-icon.png] Multiple ADH genes modulate risk for drug dependence in both African- and European-Americans.

[PMID 17273965OA-icon.png] Evidence of positive selection on a class I ADH locus.

[PMID 18331377OA-icon.png] Association of ADH and ALDH genes with alcohol dependence in the Irish Affected Sib Pair Study of alcohol dependence (IASPSAD) sample.

[PMID 18382665OA-icon.png] Ethnic related selection for an ADH Class I variant within East Asia.

[PMID 18518925OA-icon.png] Genetic susceptibility to heroin addiction: a candidate gene association study.

[PMID 18936436OA-icon.png] Prevalence in the United States of selected candidate gene variants: Third National Health and Nutrition Examination Survey, 1991-1994.

[PMID 19193628OA-icon.png] ADH single nucleotide polymorphism associations with alcohol metabolism in vivo.

[PMID 19262484] Gene-environmental interaction regarding alcohol-metabolizing enzymes in the Japanese general population.

[PMID 19526455OA-icon.png] ADH1A variation predisposes to personality traits and substance dependence.

[PMID 19737746OA-icon.png] Population differentiation as an indicator of recent positive selection in humans: an empirical evaluation.

[PMID 20089146OA-icon.png] The ADH1B Arg47His polymorphism in east Asian populations and expansion of rice domestication in history.

[PMID 20219057] ADH1B*2 allele is protective against alcoholism but not chronic liver disease in the Hungarian population.

[PMID 20700531OA-icon.png] The association of alcohol and alcohol metabolizing gene variants with diabetes and coronary heart disease risk factors in a white population.

[PMID 21303386] Alcohol-metabolizing enzyme gene polymorphisms in the Basque Country, Morocco, and Ecuador.

[PMID 21351086OA-icon.png] Shortened telomeres in individuals with abuse in alcohol consumption.

[PMID 21378355] Alcohol-dehydrogenase (ADH1B) Arg48His polymorphism in Basque Country patients with oral and laryngeal cancer: preliminary study.

[PMID 21497796OA-icon.png] Strong association of the alcohol dehydrogenase 1B gene (ADH1B) with alcohol dependence and alcohol-induced medical diseases.

[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 21895720] Alcohol dehydrogenase-1B Arg47His polymorphism and upper aerodigestive tract cancer risk: a meta-analysis including 24,252 subjects.

[PMID 21900886OA-icon.png] 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 21926110OA-icon.png] Population-specific genetic associations with oesophageal squamous cell carcinoma in South Africa.

[PMID 21968928OA-icon.png] ADH1B is associated with alcohol dependence and alcohol consumption in populations of European and African ancestry.

[PMID 22150722OA-icon.png] ADH1B polymorphism, alcohol consumption, and binge drinking in Slavic Caucasians: results from the Czech HAPIEE study.

[PMID 22325912] Determination of the effects of alcohol dehydrogenase (ADH) 1B and ADH1C polymorphisms on alcohol dependence in Turkey.


[PMID 23060937OA-icon.png] A variant allele of ADH1B and ALDH2, is associated with the risk of esophageal cancer


GET Evidence
ADH1B-H48R
aa_change His48Arg
aa_change_short H48R
impact pharmacogenetic
qualified_impact Insufficiently evaluated pharmacogenetic
overall_frequency 0.962911
summary



[PMID 23149980] Alcohol dehydrogenase and aldehyde dehydrogenase gene polymorphisms, alcohol intake and the risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition study

GWAS snp
PMID [PMID 23456092]
Trait Alcohol dependence
Title Extended genetic effects of ADH cluster genes on the risk of alcohol dependence: from GWAS to replication.
Risk Allele
P-val 3E-21
Odds Ratio 2.35 [1.95-2.84]


[PMID 23430454] Genetic variants at 4q21, 4q23 and 12q24 are associated with esophageal squamous cell carcinoma risk in a Chinese population


[PMID 23895337OA-icon.png] Alcohol-Metabolizing Genes and Alcohol Phenotypes in an Israeli Household Sample


[PMID 24164917] Childhood adversity moderates the effect of ADH1B on risk for alcohol-related phenotypes in Jewish Israeli drinkers

GWAS snp
PMID [PMID 23743675OA-icon.png]
Trait Alcohol consumption
Title A meta-analysis of two genome-wide association studies to identify novel loci for maximum number of alcoholic drinks.
Risk Allele
P-val 2E-8
Odds Ratio NR NR


[PMID 24553426OA-icon.png] Alcohol consumption and cognitive impairment in older men: A mendelian randomization study


[PMID 24552298OA-icon.png] Association Between Six Genetic Polymorphisms and Colorectal Cancer: A Meta-Analysis


[PMID 23806636OA-icon.png] Prenatal alcohol exposure and childhood atopic disease: a Mendelian randomization approach


[PMID 22560290] A comparison of Val81Met and other polymorphisms of alcohol metabolising genes in patients and controls in Northern Spain.


[PMID 22930414OA-icon.png] 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 23414439] Alcohol dehydrogenase-1B genotype (rs1229984) is a strong determinant of the relationship between body weight and alcohol intake in Japanese alcoholic men.


[PMID 25011450OA-icon.png] Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data


[PMID 25192829OA-icon.png] Testing for non-linear causal effects using a binary genotype in a Mendelian randomization study: application to alcohol and cardiovascular traits


[PMID 25323582] Alcohol dehydrogenase-1B Arg47His polymorphism is associated with head and neck cancer risk in Asian: a meta-analysis


[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 26232779] Differential Effect of Initiating Moderate Red Wine Consumption on 24-h Blood Pressure by Alcohol Dehydrogenase Genotypes: Randomized Trial in Type 2 Diabetes


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


[PMID 27902751] Exploration of a Polygenic Risk Score for Alcohol Consumption: A Longitudinal Analysis from the ALSPAC Cohort.