Variant Annotations
PharmGKB variant annotations provide information about variant-drug pairs based on individual PubMed publications. Each annotation represents information from a single paper and the goal is to report the information that the author states, not an interpretation of the paper. The PMID for supporting PubMed publications is found in the "Evidence" field.
Information presented, including study size, allele frequencies and statistics is taken directly from the publication. However, if the author does not correct p-values in cases of multiple hypotheses, curators may apply a Bonferroni correction. Curators attempt to report study size based on the actual number of participants used for the calculation of the association statistics, so the number may vary slightly from what is reported in the abstract of the paper. OMB Race Category information is derived from the paper and mapped to standardized categories. Category definitions may be found by clicking on the "OMB Race Category" link.
There are 1 annotations for this variant. Register or sign in to see them.
VIP Variant in ALDH1A1
ALDH1A1*2 is a 17bp deletion variant in the promoter region of ALDH1A1, that was first identified by Spence et al through a screening of promoter polymorphisms in diverse ethnic groups (allele frequency table included below) [Article:14506398]. The authors found no significant difference between ALDH1A1*2 expressing constructs and ALDH1A1*1 expressing constructs (the reference sequence) with luciferase assays conducted in both HeLa and HepG2 cells [Article:14506398].
Several studies have attempted to associate the presence of the ALDH1A1*2 allele with alcoholism or alcohol dependence in different populations with conflicting results. The initial discovery study found a non-statistically significant trend in the African American population linking carriers of the ALDH1A1*2 allele with alcoholism [Article:14506398]. Later studies conducted in Indo-Trinidadians seemed to support this contention, as they also observed an association between alcohol dependence and the presence of a ALDH1A1*2 allele [Article:17718398, 17286337]. In contrast, studies in Southwest California Indian tribes showed the opposite trend; namely that ALDH1A1*2 was associated with a protective effect against alcoholism [Article:17718395, 15597079]. Another study found that ALDH1A1*2 may be associated with a decreased risk of alcoholism in African Americans, contrary to the trend found in the initial discovery study [Article:17718396].
The mechanism for the effect (if any) of ALDH1A1*2 is unclear, but Spence et al suggest that it is possible that the deletion encoded by ALDH1A1*2 may eliminate a c-myb (a putative transcription factor) binding site from the promoter region of ALDH1A1 [Article:14506398].
| Population | N | Allele Frequency of ALDH1A1*1 | Allele Frequency of ALDH1A1*2 | Allele Frequency of ALDH1A1*3 | Reference |
|---|---|---|---|---|---|
| African American | 85 | 0.96 | 0.01 | 0.03 | [Article:14506398] |
| Asian American | 71 | 0.97 | 0.03 | 0 | [Article:14506398] |
| Caucasian | 239 | 0.98 | 0.02 | 0 | [Article:14506398] |
| Jewish | 36 | 0.98 | 0.02 | 0 | [Article:14506398] |
| Key Publications: | |
|---|---|
| Drugs / Other Molecules |
Chemical (3)
acetaldehyde
retinaldehyde
aldophosphamide
|
| Diseases | Alcoholism |
Appendix
Genomic Variant & GenBank ID: Deletion of 45390929-45390945 on AC_000141
GoldenPath Position: chr9:74758204-74758203 (hg18)
Publications related to rs6151031 at chr9:75568383: 4
| Relations between polymorphisms in drug-metabolising enzymes and toxicity of chemotherapy with cyclophosphamide, thiotepa and carboplatin. Pharmacogenetics and genomics. 2008. Ekhart Corine, et al. [Article:18854779@PubMed] | |
| Variations in ADH and ALDH in Southwest California Indians. Alcohol research & health : the journal of the National Institute on Alcohol Abuse and Alcoholism. 2007. Ehlers Cindy L. [Article:17718395@PubMed] | |
| Variations in alcohol-metabolizing enzymes in people of East Indian and African descent from Trinidad and Tobago. Alcohol research & health : the journal of the National Institute on Alcohol Abuse and Alcoholism. 2007. Moore Shelley, et al. [Article:17718398@PubMed] | |
| Evaluation of aldehyde dehydrogenase 1 promoter polymorphisms identified in human populations. Alcoholism, clinical and experimental research. 2003. Spence John P, et al. [Article:14506398@PubMed] |