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 3 annotations for this variant. Register or sign in to see them.
VIP Variant in UGT1A1
UGT1A1:*6
Identified in 1998 by Akaba et al., the "211G>A" (numbered with the 'a' of the start codon as 1) exon 1 polymorphism (UGT1A1*6) is the most common UGT1A1 coding variant among Asian populations, with allele frequencies in the Japanese, Korean, and Chinese populations of 0.13, 0.23, and 0.23, respectively [Article:9784835]. The variant is virtually absent in Caucasian populations and populations of African origin [Article:10975608, 15572581]. The UGT1A1*28 promoter variant has a lower frequency in Asian populations, ranging from 0.07 in the Japanese to 0.143 in the Taiwanese [Article:9731723, 9929972, 9784835]. However, the high occurrence of hyperbilirubinemia, frequency of the UGT1A1*6 variant and its effect on UGT1A1 expression (in the homozygous state, 32% that of wildtype) [Article:9630669] implicate the role of this variant in Gilbert syndrome in Asian populations. The SN-38 (a metabolite of irinotecan) glucuronidation efficiency ratio of UGT1A1*6 was found to be 47% that of wildtype, indicating individuals with this variant may have a reduced capacity to metabolize SN-38 and may suffer from irinotecan toxicity [Article:12485959].
| Key Publications: | |
|---|---|
| Drugs / Other Molecules |
Drug (6)
|
| Diseases | Gilbert's syndrome 11 12 13 Jaundice, Neonatal 14 |
| Phenotype |
|
Appendix
gp position: chr2:234333883(hg18)
Genomic Variant & GenBank ID: 601898 G>A on NT_005120
mRNA Variant & GenBank ID: 226G>A on NM_000463
Protein Variant & GenBank ID: 71Gly>Arg on NP_000454
Connected Drugs
Connected Drug Classes
| Evidence | Drug Class |
|---|---|
| VIP Annotation | estrogens |
| VIP Annotation | thyroid hormones |
Connected Diseases
| Evidence | Disease |
|---|---|
| Gilbert's syndrome | |
| Jaundice, Neonatal | |
| Neoplasms |
Publications related to rs4148323 at chr2:234669144: 10
Cross-References
- UCSC Golden Path:
- chr2:234669144
- dbSNP:
- rs4148323
- ALFRED:
- SI000426M
- HapMap:
- rs4148323
- JSNP:
- ssj0003452
Platform Availability
- Affymetrix
- Illumina