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 4 annotations for this variant. Register or sign in to see them.
VIP Variant in CYP2A6
rs28399454 (5065 G>A) is present within the CYP2A6*17 allele. A significant association between efavirenz pharmacokinetic parameters and CYP2A6 is observed when individuals with one or more copies of CYP2A6*9b (rs8192726) and CYP2A6*17 (rs28399454) were grouped together, but not when rs28399454 was analyzed individually [Articles:19371316, 20860463]. In multiple regression analysis, incorporating multiple variants, CYP2A6 rs8192726 and/ or rs28399454 status independently contributes to efavirenz inter-individual plasma concentrations, accounting for around 10% (8.6-12%), with CYP2B6 rs3745274 genotype TT contributing 36-45.2%, and UGT2B7 *1a genotype also significantly contributing [Article:19371316; 19779319].
CYP2A6*17 (defined by the variant rs28399454, V365M) is found at a frequency of around 10% in Black individuals, but not identified in White, Korean or Japanese individuals [Article:16952495; 15592323].
Please note; several other variants also make up the CYP2A6*9b and CYP2A6*17 alleles, as defined by the CYP-450 nomenclature committee: http://www.cypalleles.ki.se/cyp2a6.htm. See the CYP2A6 haplotype sheet for more details.
The CYP2A6 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 and haplotypes will differ (in a complementary manner) from those in this VIP summary that are given on the minus strand as reported in the literature.
| Key Publications: | |
|---|---|
| Drugs / Other Molecules |
Publications related to rs28399454 at chr19:41351267: 6
Cross-References
- UCSC Golden Path:
- chr19:41351267
- dbSNP:
- rs28399454
- HapMap:
- rs28399454
- LS-SNP:
- rs28399454
Platform Availability
- Illumina