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 12 annotations for this variant. Register or sign in to see them.
There are 1 disease-related annotations for this variant. Register or sign in to see them.
VIP Variant in CYP2B6
The CYP2B6:983T>C variant was reported in a large screen of CYP gene polymorphisms by Solus et al., 2004 [Article:15469410]. It occurs with an allele frequency of 4-9% in Blacks and African Americans and was not observed in Asians and Caucasians [Article:16272958, 17235330, 17391322]. It was shown at low frequency (1.1%) in Hispanic Americans in one study [Article:17391322]. This variant is found in linkage with intronic variants 17897C>T, 18273G>A and 18627G>A and with Lys262Arg in the CYP2B6*16 allele but is the only protein coding change in the CYP2B6*18 allele. Expression of CYP2B6*18 in COS-1 cells resulted in no detectable protein (Klein et al., [Article:16272958]). Klein et al. also suggested that Ile328 resides within an alpha helix and the change in hydrophobicity from hydrophobic isoleucine to the polar but uncharged threonine may disrupt helix formation. Wang et al. found no change in catalytic activity of this variant with the substrate bupropion but observed much lower expression of the 983T>C variant (15-30% as compared to wild type [Article:16272958]). Wang et al. also showed that when expressed with the Lys262Arg (785A>G) variant, as the CYP2B6*16 allele, the expression was higher as compared to 983T>C alone [Article:16495778]. This residue is also highly conserved across alignments with other P450s [Article:16272958]. Presence of this allele is associated with high plasma drug concentrations in patients treated with efavirenz [Article:17235330, 18281305] and nevirapine [Article:18281305]. In a recent study the composite CYP2B6:516G>T/983T>C genotype was significantly associated with plasma drug exposure and clearance for efavirenz but not nevirapine [Article:19239339].
| Key Publications: | |
|---|---|
| Drugs / Other Molecules |
Drug (3)
|
| Diseases | HIV |
Appendix
| mRNA Variant & GenBank ID: | 990T>C on NM_000767.4 |
|---|---|
| Protein Variant & GenBank ID: | Ile328Thr on NP_000758.1 |
Publications related to rs28399499 at chr19:41518221: 14
Cross-References
- UCSC Golden Path:
- chr19:41518221
- dbSNP:
- rs28399499
- HapMap:
- rs28399499
Platform Availability
- Illumina