Important Variant Information for SLCO1B1
Submitted by: Lara Mangravite (PARC)
Reviewed by: Reviewed
Submitted date: June 23, 2006
There are Three Important Variants for SLC01B1.
| Gene HGNC Name: | SLCO1B1 |
|---|---|
| Variant Summary: | Estimated allelic frequencies for this variant are N130=0.70 and D130=0.30 for European Americans (n=49), N130=0.26 and D130=0.74 for African Americans (n=22), N130=0.371 and D130=0.629 in Japanese (n=120). In vitro studies indicate that function of N130D (SLCO1B1*1B) is indistinguishable from that of wild-type transporter (encoded by SLCO1B1*1A). In vivo pharmacokinetic studies are conflicting but suggest that carriers of N130D exhibit decreased pravastatin plasma AUC. The expectation is that this is caused by increased hepatocellular clearance due to reduced transporter function. |
| Key PubMed IDs: | 11477075, 12811365, 15116054, 15564882, 16198652 |
| Genomic Variant & GenBank ID: | 14,088,712 A>G on NT_009714 |
| mRNA Variant & GenBank ID: | 522 A>G on NM_006446 |
| Protein Variant & GenBank ID: | 130 N>D on NP_006437 |
| dbSNP rs#: | rs2306283 |
| GoldenPath Position: | Chr12: 21,221,005 (hg18) |
| Key Drugs/Substrates: | Same as wild type |
| Key Haplotypes: | SLCO1B1*1B, SLCO1B1*15, SLCO1B1*17 |
| Gene HGNC Name: | SLCO1B1 |
|---|---|
| Variant Summary: | Estimated allele frequencies for this variant are listed as V174=0.86 and A174=0.14 in European Americans (n=49), V174=0.98 and A174=0.02 in African Americans (n=22), V174=0.842 and A174=0.158 in Japanese (n=120). In vitro results are conflicting but suggest that this variant results in reduced transporter function (Vmax ), possibly due to intracellular sequestration. In vivo pharmacokinetic studies are conflicting but suggest that carriers of V174A exhibit increased pravastatin plasma AUC. The expectation is that this is caused by decreased hepatocellular clearance due to reduced transporter function. Similar increases in AUC were reported for T521C carriers exposed to fexofenadine or repaglinide, though neither of these drugs is a proven substrate of SLCO1B1. |
| Key PubMed IDs: | 11477075, 12811365, 15970799, 15564882, 12130747, 15226675, 15116054, 15548849, 16198652, 15842561, 15961978 |
| Genomic Variant & GenBank ID: | 14,090,523 T>C on NT_009714 |
| mRNA Variant & GenBank ID: | 655 T>C on NM_006446 |
| Protein Variant & GenBank ID: | 174 V>A on NP_006437 |
| dbSNP rs#: | rs4149056 |
| GoldenPath Position: | Chr12:21,222,816 (hg18) |
| Key Drugs/Substrates: | Same as wild type |
| Key Haplotypes: | SLCO1B1*5, SLCO1B1*15, SLCO1B1*17 |
| Gene HGNC Name: | SLCO1B1 |
|---|---|
| Variant Summary: | This is a promoter variant, termed G-11187A. Estimated allelic frequency is G-11187=0.93 and A-11187=0.07 in a Caucasian population (n=41). Carriers of A-11187 exhibited elevated pravastatin plasma AUC and increased pravastatin half-life compared to non-carriers. This was accompanied by reduced hepatocellular pravastatin-induced inhibition of cholesterol synthesis, suggesting lower hepatocellular pravastatin concentrations. Elevated plasma AUC has also been reported in G-11187A carriers exposed to fexofenadine but not repaglinide, though neither of these drugs are proven substrates of SLCO1B1. This variant is found in conjunction with N130D and V174A. |
| Key PubMed IDs: | 15226675, 15864131, 15842561, 15961978 |
| Genomic Variant & GenBank ID: | 14,042,296 G>A on NT_009714 |
| mRNA Variant & GenBank ID: | Not Relevant |
| Protein Variant & GenBank ID: | Not Relevant |
| dbSNP rs#: | rs4149015 |
| GoldenPath Position: | Chr12:21,174,589 (hg18) |
| Key Drugs/Substrates: | Same as wild type |
| Key Haplotypes: | SLCO1B1*17 |