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 30 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 UGT1A1
UGT1A1*1
(TA)6 repeat (wildtype)
UGT1A1*28
Genomic Variant & GenBank ID: 601635 (TA)6TAA -> (TA)7TAA on NT_005120 (601635 T > TAT on NT_005120).
The UGT1A1*28 (TA)6 -> (TA)7 promoter variation is the most extensively studied variant of UGT1A1. Identified in 1995 by Bosma et al., the UGT1A1*28 results in a reduced level of UGT1A1 transcription as compared to the (TA)6 wildtype allele [Article:7565971]. The UGT1A1 promoter length is highly variable across populations, with the allele frequency of UGT1A1*28 from 0.09-0.16 in Asian populations, 0.26-0.31 in Caucasian populations and 0.42-0.56 in populations of African ancestry [Articles:10591539, 9653159]. The UGT1A1*28 variant forms the genetic basis of Gilbert syndrome, although its presence is required but not sufficient to manifest the mild unconjugated hyperbilirubinemia of the disorder [Articles:7565971, 8596320]. The UGT1A1*28 variant has also been associated with reduced glucuronidation of SN-38 (a metabolite of irinotecan) and severe toxicity with irinotecan treatment [Articles:9466980, 11156391, 11990381, 15297419] as well as hyperbilirubinemia with administration of tranilast [Article:14647407] and atazanavir [Article:16118329].
UGT1A1*36
Genomic Variant & GenBank ID: 601635 (TA)6TAA > (TA)5TAA on NT_005120 (601635 T> (-) or 601635delTA on NT_005120).
Described in 1998 (Di Rienzo et al., Clin Pharmacol Ther 63:207), UGT1A1*36 has been shown to result in increased transcriptional activity of UGT1A1 as compared to the (TA)6 wildtype (UGT1A1*1) [Articles:9653159, 10591539]. The UGT1A1*36 allele occurs almost exclusively in populations of African origin, with an estimated allele frequency of 0.03-0.10 [Articles:9653159, 10591539, 15388579].
UGT1A1*37
Genomic Variant & GenBank ID: 601635 (TA)6TAA -> (TA)8TAA on NT_005120 (601635 T>TATAT on NT_005120).
Described in 1998 (Di Rienzo et al., Clin Pharmacol Ther 63:207), UGT1A1*37 has been shown to result in decreased transcriptional activity of UGT1A1 as compared to the (TA)6 wildtype (UGT1A1*1) [Articles:9653159, 10091406]. The UGT1A1*37 allele occurs almost exclusively in populations of African origin, with an estimated allele frequency of 0.02-0.07 [Articles:9653159, 10591539, 15388579].
| Key Publications: | |
|---|---|
| Drugs / Other Molecules |
Drug (6)
|
| Diseases | Gilbert's syndrome 11 12 Hyperbilirubinemia 13 14 Jaundice, Neonatal 15 |
| Phenotype |
|
| Phenotype Datasets | Irinotecan Clinical Data |
Appendix
gp position: chr2:234333620 (hg18)
Connected Drugs
| Evidence | Drug |
|---|---|
| atazanavir | |
| etoposide | |
| fluorouracil | |
| irinotecan | |
| leucovorin | |
| SN-38 | |
| Tipifarnib | |
| tranilast |
Connected Drug Classes
| Evidence | Drug Class |
|---|---|
| VIP Annotation | estrogens |
| VIP Annotation | thyroid hormones |