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^-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 18996923]

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.

[PMID 19298322] 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 19687126] 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 21437268] 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 21940907] 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)