Important Haplotype Information for SLCO1B1
Submitted by: Lara Mangravite (PARC)
Reviewed by: Reviewed
Submitted date: June 23, 2006
There are Five Important Haplotypes for SLC01B1.
| Gene HGNC Name: | SLCO1B1 |
|---|---|
| Haplotype Significance: | Wild Type SLCO1B1 |
| Does this haplotype span more than one gene? | No |
| Definitive Publication or Website: | Polymorphisms in OATP-C: identification of multiple allelic variants associated with altered transport activity among European- and African-Americans. Tirona RG, Leake BF, Merino G, Kim RB. J Biol Chem. 2001 Sept 21;276(38):35669-75 [PMID: 11477075]. |
| Key PubMed IDs: | 11477075 |
| How many SNPs, indels, repeats define this haplotype? | Zero |
| Gene HGNC Name: | SLCO1B1 |
|---|---|
| Haplotype Significance: | Presence of SLCO1B1*1B was associated with reduced pravastatin plasma AUC [PMID: 15226675]. |
| Does this haplotype span more than one gene? | No |
| Definitive Publication or Website: | Polymorphisms in OATP-C: identification of multiple allelic variants associated with altered transport activity among European- and African-Americans. Tirona RG, Leake BF, Merino G, Kim RB. J Biol Chem. 2001 Sept 21;276(38):35669-75 [PMID: 11477075]. |
| Key PubMed IDs: | 15226675, 11477075 |
| How many SNPs, indels, repeats define this haplotype? | One: N130D |
| Gene HGNC Name: | SLCO1B1 |
|---|---|
| Haplotype Significance: | SLCO1B1*5 is comprised of a single variant (V174A). In vitro studies suggest that function is lower for this variant than for SLCO1B1*1A, possibly due to intracellular sequestration [PMID: 11477075, 15970799, 15564882, 12130747]. In vivo pharmacokinetic studies suggest that this results in increased systemic exposure, as measured by plasma AUC, for pravastatin and possibly also results in attenuated cholesterol response [PMID: 15226675, 15116054, 15548849, 12811365]. |
| Does this haplotype span more than one gene? | No |
| Definitive Publication or Website: | Polymorphisms in OATP-C: identification of multiple allelic variants associated with altered transport activity among European- and African-Americans. Tirona RG, Leake BF, Merino G, Kim RB. J Biol Chem. 2001 Sept 21;276(38):35669-75 [PMID:11477075]. |
| Key PubMed IDs: | 11477075, 15970799, 15564882, 12130747, 15226675, 15116054, 15548849, 12811365 |
| How many SNPs, indels, repeats define this haplotype? | One: V174A |
| Gene HGNC Name: | SLCO1B1 |
|---|---|
| Haplotype Significance: | Carriers of SLCO1B1*15 may have reduced hepatocellular transport and, therefore, increased systemic exposure to clinical drugs that are SLCO1B1 substrates, in particular pravastatin [PMID: 15970799, 15226675, 15564882, 12811365]. The same may be true for bilirubin and for SN-38, the metabolite of irinotecan [PMID: 15608127, 15519273]. |
| Does this haplotype span more than one gene? | No |
| Definitive Publication or Website: | Polymorphisms of OATP-C (SLC21A6) and OAT3 (SLC22A8) genes: consequences for pravastatin pharmacokinetics. Nishizato Y, Ieiri I, Suzuki H, Kimura M, Kawabata K, Hirota T, Takane H, Irie S, Kusuhara H, Urasaki Y, Urae A, Higuchi S, Otsubo K, Sugiyama Y. Clin Pharmacol Ther. 2003 Jun;73 (6):554-65 [PMID: 12811365]. |
| Key PubMed IDs: | 15970799, 15226675, 15564882, 12811365, 15608127, 15519273 |
| How many SNPs, indels, repeats define this haplotype? | Two: N130D, V174A |
| Gene HGNC Name: | SLCO1B1 |
|---|---|
| Haplotype Significance: | Carriers of this haplotype may exhibit increased plasma pravastatin concentrations and decreased hepatocellular pravastatin concentrations, causing reduced cholesterol reduction. These findings are preliminary in nature. |
| Does this haplotype span more than one gene? | No |
| Definitive Publication or Website: | Acute effects of pravastatin on cholesterol synthesis are associated with SLCO1B1 (encoding OATP1B1) haplotype *17. Niemi M, Neuvonen PJ, Hofmann U, Backman JT, Schwab M, Lutjohann D, von Bergmann K, Eichelbaum M, Kivisto KT. Pharmacogenet Genomics. 2005 May 15;(5):303-9 [PMID: 15864131]. |
| Key PubMed IDs: | 15864131 |
| How many SNPs, indels, repeats define this haplotype? | Three: N130D, V174A, G-11187A |