Important Variant Information for ALDH1A1
Submitted by: Ryan Owen (PharmGKB)
Reviewed by: Under Review
Submitted date: Feb 21, 2008
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There are Two Important Variants for ALDH1A1.
| Gene HGNC Name: | ALDH1A1 |
|---|---|
| Variant Summary: | 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) [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[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[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 [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 [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 [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[14506398]. |
| Key PubMed IDs: | 14506398 17718398 17718395 |
| Genomic Variant & GenBank ID: | Deletion of 45390929-45390945 on AC_000141 |
| mRNA Variant & GenBank ID: | N/A |
| Protein Variant & GenBank ID: | N/A |
| dbSNP rs#: | rs6151031 |
| GoldenPath Position: | chr9:74758204-74758203 (hg18) |
| Key Drugs/Substrates: | acetaldehyde , retinaldehyde, aldophosphamide |
| Key Phenotypes/Diseases: | Alcoholism |
| Gene HGNC Name: | ALDH1A1 |
|---|---|
| Variant Summary: | ALDH1A1*3 is a 3bp insertion 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) [14506398]. In contrast to ALDH1A1*2, which was found at low frequencies in every ethnic group examined by Spence et al, ALDH1A1*3 was found specifically in African Americans[14506398]. In vitro luciferase studies in HeLa and HepG2 cell lines suggest that ALDH1A1*3 has significantly lower expression than ALDH1A1*1 (the reference sequence)[14506398]. This suggests that ALDH1A1*3 may not be transcribed as efficiently, and may lead to a reduction in function [14506398] . In seeming agreement with this contention, Spence et al found that the frequency of ALDH1A1*3 was significantly higher among African American alcoholics[14506398] . However, a later study by Scott et al suggested that ALDH1A1*3 actually had a protective effect against alcoholism [17718396]. |
| Key PubMed IDs: | 14506398 17718396 |
| Genomic Variant & GenBank ID: | Insertion between 45391035-45391035 on AC_000141 |
| mRNA Variant & GenBank ID: | N/A |
| Protein Variant & GenBank ID: | N/A |
| dbSNP rs#: | N/A |
| GoldenPath Position: | insertion between chr9:74758298-74758297 (hg18) |
| Key Drugs/Substrates: | acetaldehyde , retinaldehyde, aldophosphamide |
| Key Phenotypes/Diseases: | Alcoholism |
| 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 | 14506398 |
| Asian American |
71 | 0.97 | 0.03 | 0 | 14506398 |
| Caucasian | 239 | 0.98 | 0.02 | 0 | 14506398 |
| Jewish | 36 | 0.98 | 0.02 | 0 | 14506398 |