VIP Variant in ADH1B
Note: The ADH1B gene is found on the minus chromosomal strand. Please note that for standardization, the PharmGKB presents all allele base pairs on the positive chromosomal strand, therefore the alleles within our variant annotations will differ (in a complementary manner) from those in this VIP summary that are given on the minus strand as reported in the literature.
ADH1B*2 (Arg47His in exon 3) has been shown in vitro to metabolize ethanol to acetaldehyde more quickly than the *1 allele. [Article:17295732]. It has a Vmax about 40 times that of the *1 allele [Article:16571603]. 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) [Article:10441588].
The ADH1B*2 allele is the predominant allele in Asian populations [Article:10441588]. Within Asians, the *2 allele was more common among non-alcoholics than alcoholics, with similar findings in other populations. [Article:15099407]. However there are indications that if those with the *2 genotype continue to drink in spite of the adverse reactions, they could be at risk for liver damage due to increased levels of acetaldehyde [Article:15099407]. But no conclusive evidence of liver disease and ADH genotype has been found to date [Article:16792560].
| Key Publications: | |
|---|---|
| Drugs / Other Molecules |
Drug (1)
|
| Diseases | Alcoholism |
Appendix
Note: The ADH1B*2 allele is represented by these reference sequences.
| Genomic Variant & GenBank ID: | NT_016354 |
|---|---|
| mRNA Variant & GenBank ID: | NM_000668 |
| Protein Variant & GenBank ID: | NP_000659 |
| GoldenPath Position: | chr4:100458342 (hg18) |
Publications related to rs1229984 at chr4:100239319: 3
| Alcohol dehydrogenase genetic polymorphisms, low-to-moderate alcohol consumption, and risk of breast cancer. Alcoholism, clinical and experimental research. 2007. Visvanathan Kala, et al. [Article:17295732@PubMed] | |
| Overview of the role of alcohol dehydrogenase and aldehyde dehydrogenase and their variants in the genesis of alcohol-related pathology. The Proceedings of the Nutrition Society. 2004. Crabb David W, et al. [Article:15099407@PubMed] | |
| Interaction between the functional polymorphisms of the alcohol-metabolism genes in protection against alcoholism. American journal of human genetics. 1999. Chen C C, et al. [Article:10441588@PubMed] |
Cross-References
- UCSC Golden Path:
- chr4:100239319
- dbSNP:
- rs1229984
- ALFRED:
- SI000229N
- HapMap:
- rs1229984
- JSNP:
- ssj0002065
Platform Availability
- Illumina