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 7 annotations for this variant. Register or sign in to see them.
VIP Variant in AHR
Kawajiri et al first identified the R554K variant of AHR, which occurs at a high frequency in the Japanese population; the authors did not observe any association between the R554K variant and the incidence of lung cancer [Article:7550366]. Smart and Daly [Article:10739168] later observed a difference between reference AHR and AHR-R455K in their ability to induce the transcription of CYP1A1 when treated with the AHR substrate 3-methylcholanthrene (MC). One year later, Wong et al [Article:11207035] did not observe the same result when they used 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as the substrate to active AHR. Wong et al also determined the allele frequency of AHR-R455K in several different populations (see allele frequency table below).
Since those initial reports, most association studies have been negative. AHR-R554K was not found to be associated with Alzheimer's Disease [Article:12852830], bladder cancer [Article:11866883], or interindividual differences in the expression of CYP1A1 [Article:11505220]. A recent functional study found no difference between reference sequence AHR and AHR-R455K in either AHR mRNA or protein expression, although some lower frequency (and far less studied) variants were identified as having reduced AHR protein expression [Article:15860653].
| Population | Allele Frequency of 554K | Reference |
|---|---|---|
| Japanese | 0.43 | [Article:7550366] |
| Ivory Coast African | 0.57 | [Article:11207035] |
| African | 0.53 | [Article:11207035] |
| Caribbean African | 0.39 | [Article:11207035] |
| Canadian Chinese | 0.32 | [Article:11207035] |
| Native Indian | 0.14 | [Article:11207035] |
| French Canadian | 0.12 | [Article:11207035] |
| North American (mixed ethnicities) | 0.11 | [Article:11207035] |
| Canadian Inuit | 0.09 | [Article:11207035] |
| German | 0.07 | [Article:11207035] |
| Key Publications: | |
|---|---|
| Drugs / Other Molecules |
Chemical (2)
2,3,7,8-tetrachlorodibenzo-p-dioxin
3-methylcholanthrene
|
Appendix
1. AHR:R554K
| Genomic Variant & GenBank ID: | G17265602A on AC_000139 |
|---|---|
| mRNA Variant & GenBank ID: | G1661A on NM_001621 |
| Protein Variant & GenBank ID: | R554K on NP_001612 |
| GoldenPath Position: | chr7:17345635 on hg18 |
Connected Drug Classes
| Evidence | Drug Class |
|---|---|
| Variant Annotation | xenobiotics |
Connected Diseases
| Evidence | Disease |
|---|---|
| Alzheimer Disease | |
| Lung Neoplasms | |
| Urinary Bladder Neoplasms |
Publications related to rs2066853 at chr7:17379110: 7
Cross-References
- UCSC Golden Path:
- chr7:17379110
- dbSNP:
- rs2066853
- ALFRED:
- SI000370K
- HapMap:
- rs2066853
Platform Availability
- Affymetrix
- Illumina