{{Rsnum
|rsid=1229984
|Gene=ADH1B
|Chromosome=4
|position=99318162
|Orientation=minus
|ReferenceAllele=A
|MissenseAllele=G
|GMAF=0.2117
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(A;A)
|geno2=(A;G)
|geno3=(G;G)
|Gene_s=ADH1B
}}{{ population diversity
| geno1=(A;A)
| geno2=(A;G)
| geno3=(G;G)
| CEU | 0.0 | 0.0 | 100.0
| HCB | 57.8 | 37.8 | 4.4
| JPT | 52.3 | 43.2 | 4.5
| YRI | 0.0 | 0.0 | 100.0
| ASW | 0.0 | 0.0 | 0.0
| CHB | 57.8 | 37.8 | 4.4
| CHD | 0.0 | 0.0 | 0.0
| GIH | 0.0 | 0.0 | 0.0
| LWK | 0.0 | 0.0 | 0.0
| MEX | 0.0 | 0.0 | 0.0
| MKK | 0.0 | 0.0 | 0.0
| TSI | 0.0 | 0.0 | 0.0
| HapMapRevision=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|21968928}}

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<sup>-10</sup>) 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.[http://www.cdc.gov/genomics/hugenet/file/print/reviews/alcohol.pdf]

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|18996923|OA=1
}}

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]].

{{omim
|desc=ALCOHOL DEHYDROGENASE, BETA SUBUNIT, &apos;TYPICAL&apos;/&apos;ATYPICAL&apos;
|id=103720
|quiet=1
|rsnum=1229984
|variant=0001
}}

{{PMID Auto
|PMID=19298322
|Title=Associations and Interactions Between SNPs in the Alcohol Metabolizing Genes and Alcoholism Phenotypes in European Americans.
|OA=1
}}

According to [https://www.23andme.com/you/community/thread/1144/ 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 Auto
|PMID=19687126
|Title=A non-synonymous variant in ADH1B is strongly associated with prenatal alcohol use in a European sample of pregnant women
|OA=1
}}
{{PMID Auto
|PMID=19698717
|Title=Functional variants in ADH1B and ALDH2 coupled with alcohol and smoking synergistically enhance esophageal cancer risk
}}

{{PharmGKB
|RSID=rs1229984
|Name_s=ADH1B*2; ADH1B: Arg47His
|Gene_s=ADH1B
|Feature=Exon/NonSyn
|Evidence=Web Resource:http://www.pharmgkb.org/search/annotatedGene/adh1b/variant.jsp
|Annotation=This allele has been repeatedly reported to protect against alcoholism or alcohol use disorders (AUD) due to increased sensitivity to alcohol. The higher levels of accumulated acetaldehyde seem to be responsible for uncomfortable symptoms such as flushing, headaches, nausea that carriers of the *2 allele experience (especially homozygotes).
|Drugs=ethanol
|Drug Classes=
|Diseases=
|Curation Level=In-Depth
|PharmGKB Accession ID=PA161845832
}}

{{PMID Auto
|PMID=19861527
|Title=Impact of multiple alcohol dehydrogenase gene polymorphisms on risk of upper aerodigestive tract cancers in a Japanese population
}}

{{PMID Auto
|PMID=20205700
|Title=Genetic determinants of both ethanol and acetaldehyde metabolism influence alcohol hypersensitivity and drinking behaviour among Scandinavians
}}

{{PMID Auto
|PMID=20158305
|Title=Associations between ADH gene variants and alcohol phenotypes in Dutch adults
}}
{{PMID Auto
|PMID=20833657
|Title=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 Auto
|PMID=21372407
|Title=Confirmation of ALDH2 as a Major Locus of Drinking Behavior and of Its Variants Regulating Multiple Metabolic Phenotypes in a Japanese Population
}}

{{PMID Auto
|PMID=21437268
|Title=A Genome-Wide Association Study of Upper Aerodigestive Tract Cancers Conducted within the INHANCE Consortium
|OA=1
}}

{{PMID Auto
|PMID=22144473
|Title=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 Auto
|PMID=21940907
|Title=Joint effects of alcohol consumption and polymorphisms in alcohol and oxidative stress metabolism genes on risk of head and neck cancer
|OA=1
}}

{{PMID Auto
|PMID=22690706
|Title=Association of alcohol dehydrogenase polymorphisms and lifestyle factors with excessive alcohol intake within the Spanish population (EPIC-Spain)
}}

{{ClinVar
|rsid=1229984
|Reversed=1
|FwdREF=A
|FwdALT=G
|REF=T
|ALT=C
|RSPOS=100239319
|CHROM=4
|GMAF=0.2111
|dbSNPBuildID=87
|SSR=0
|SAO=1
|VP=0x05037800000015051f130101
|GENEINFO=ADH1B:125
|GENE_NAME=ADH1B
|GENE_ID=125
|WGT=0
|VC=SNV
|CLNALLE=1
|CLNHGVS=NC_000004.11:g.100239319T>C
|CLNSRC=OMIM Allelic Variant
|CLNORIGIN=1
|CLNSRCID=103720.0001
|CLNSIG=255
|CLNCUI=CN028882
|CLNDBN=Alcohol dependence; AERODIGESTIVE TRACT CANCER, SQUAMOUS CELL, ALCOHOL-RELATED, PROTECTION AGAINST
|Disease=Alcohol dependence; AERODIGESTIVE TRACT CANCER
|CLNACC=RCV000019813.1; RCV000019814.1
|Tags=RV;PM;TPA;PMC;S3D;SLO;VLD;G5;HD;GNO;KGPhase1;KGPilot123;KGPROD;OTHERKG;PH3;LSD;MTP;OM
|CAF=0.2117; 0.7883
|CLNDSDB=MedGen:OMIM
|CLNDSDBID=CN028882:103780
|COMMON=1
}}

{{PMID|12050823|OA=1
}} A global perspective on genetic variation at the ADH genes reveals unusual patterns of linkage disequilibrium and diversity.

{{PMID|16255080|OA=1
}} A haplotype map of the human genome.

{{PMID|16685648|OA=1
}} Diplotype trend regression analysis of the ADH gene cluster and the ALDH2 gene: multiple significant associations with alcohol dependence.

{{PMID|17185388|OA=1
}} Multiple ADH genes modulate risk for drug dependence in both African- and European-Americans.

{{PMID|17273965|OA=1
}} Evidence of positive selection on a class I ADH locus.

{{PMID|18331377|OA=1
}} Association of ADH and ALDH genes with alcohol dependence in the Irish Affected Sib Pair Study of alcohol dependence (IASPSAD) sample.

{{PMID|18382665|OA=1
}} Ethnic related selection for an ADH Class I variant within East Asia.

{{PMID|18518925|OA=1
}} Genetic susceptibility to heroin addiction: a candidate gene association study.

{{PMID|18936436|OA=1
}} Prevalence in the United States of selected candidate gene variants: Third National Health and Nutrition Examination Survey, 1991-1994.

{{PMID|19193628|OA=1
}} 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|19526455|OA=1
}} ADH1A variation predisposes to personality traits and substance dependence.

{{PMID|19737746|OA=1
}} Population differentiation as an indicator of recent positive selection in humans: an empirical evaluation.

{{PMID|20089146|OA=1
}} 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|20700531|OA=1
}} 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|21351086|OA=1
}} 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|21497796|OA=1
}} 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|21900886|OA=1
}} 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|21926110|OA=1
}} Population-specific genetic associations with oesophageal squamous cell carcinoma in South Africa.

{{PMID|21968928|OA=1
}} ADH1B is associated with alcohol dependence and alcohol consumption in populations of European and African ancestry.

{{PMID|22150722|OA=1
}} 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 Auto
|PMID=23060937
|Title=A variant allele of ADH1B and ALDH2, is associated with the risk of esophageal cancer
|OA=1
}}

{{GET Evidence
|gene=ADH1B
|aa_change=His48Arg
|aa_change_short=H48R
|impact=pharmacogenetic
|qualified_impact=Insufficiently evaluated pharmacogenetic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs1229984
|overall_frequency_n=10359
|overall_frequency_d=10758
|overall_frequency=0.962911
|n_genomes=49
|n_genomes_annotated=0
|n_haplomes=95
|n_articles=0
|n_articles_annotated=0
|qualityscore_in_silico=1
|qualitycomment_in_silico=Y
|in_gwas=Y
|in_pharmgkb=Y
|nblosum100=1
|autoscore=2
|webscore=N
}}

{{PMID Auto
|PMID=23149980
|Title=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
}}

{{PMID Auto GWAS
  |PMID=23456092
  |Trait=Alcohol dependence
  |Title=Extended genetic effects of ADH cluster genes on the risk of alcohol dependence: from GWAS to replication.
  |RiskAllele=
  |Pval=3E-21
  |OR=2.35
  |ORtxt=[1.95-2.84]
  }}

{{PMID Auto
|PMID=23430454
|Title=Genetic variants at 4q21, 4q23 and 12q24 are associated with esophageal squamous cell carcinoma risk in a Chinese population
}}

{{PMID Auto
|PMID=23895337
|Title=Alcohol-Metabolizing Genes and Alcohol Phenotypes in an Israeli Household Sample
}}

{{PMID Auto
|PMID=24164917
|Title=Childhood adversity moderates the effect of ADH1B on risk for alcohol-related phenotypes in Jewish Israeli drinkers
}}

{{PMID Auto GWAS
  |PMID=23743675
  |Trait=Alcohol consumption
  |Title=A meta-analysis of two genome-wide association studies to identify novel loci for maximum number of alcoholic drinks.
  |RiskAllele=
  |Pval=2E-8
  |OR=NR
  |ORtxt=NR
  }}

{{PMID Auto
|PMID=24553426
|Title=Alcohol consumption and cognitive impairment in older men: A mendelian randomization study
}}

{{PMID Auto
|PMID=24552298
|Title=Association Between Six Genetic Polymorphisms and Colorectal Cancer: A Meta-Analysis
}}

{{PMID Auto
|PMID=23806636
|Title=Prenatal alcohol exposure and childhood atopic disease: a Mendelian randomization approach
|OA=1
}}

{{PMID Auto
|PMID=22560290
|Title=A comparison of Val81Met and other polymorphisms of alcohol metabolising genes in patients and controls in Northern Spain.
}}

{{PMID Auto
|PMID=22930414
|Title=Single nucleotide polymorphisms of ADH1B, ADH1C and ALDH2 genes and esophageal cancer: a population-based case-control study in China.
}}

{{PMID Auto
|PMID=23088731
|Title=Tag single nucleotide polymorphisms of alcohol-metabolizing enzymes modify the risk of upper aerodigestive tract cancers: HapMap database analysis.
}}

{{PMID Auto
|PMID=23414439
|Title=Alcohol dehydrogenase-1B genotype (rs1229984) is a strong determinant of the relationship between body weight and alcohol intake in Japanese alcoholic men.
}}

{{PMID Auto
|PMID=25011450
|Title=Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data
}}

{{PMID Auto
|PMID=25192829
|Title=Testing for non-linear causal effects using a binary genotype in a Mendelian randomization study: application to alcohol and cardiovascular traits
}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}