Rapid identification of three functionally relevant polymorphisms in the OATP1B1 transporter gene using Pyrosequencing

Pharmacogenomics
Maren RohrbacherJörn Lötsch

Abstract

Clinical evidence suggests there are three single nucleotide polymorphisms (SNPs) of the solute carrier organic anion transporter family member B1 (SLCO1B1) gene for which in vivo evidence for a functional relevance for organic anion transporter polypeptides subgroup C (OATP1B1, formerly OATP-C) has been provided. These genetic variants have been shown to lead to altered pharmacokinetics of OATP1B1 substrates, mainly pravastatin, but also the irinotecan metabolite SN-38, estrone-3-sulfate, and estradiol-17beta-glucuronide. The authors therefore developed reliable and quick screening assays to identify the SLCO1B1 SNPs -11187G>A, 388A>G and 521T>C, in order to facilitate the judgment of their clinical role and to identify allelic frequencies of SNPs and haplotypes in a Caucasian random sample. Three simplex Pyrosequencing assays were developed and the three selected SLCO1B1 SNPs were screened for in 250 DNA samples from healthy young female and male unrelated volunteers of Caucasian ethnicity. SLCO1B1 haplotypes involving DNA positions -11187, 388 and 521 were identified by in silico haplotyping. A clear identification of the three single nucleotide polymorphisms in the 250 DNA samples was possible and was verified by routine im...Continue Reading

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Citations

Jun 2, 2011·European Journal of Clinical Pharmacology·Eleni AklilluJohanna Weiss
Nov 12, 2014·Annual Review of Medicine·Daniel L Hertz, James Rae
Nov 13, 2007·Clinica Chimica Acta; International Journal of Clinical Chemistry·Eun-Young KimSang-Goo Shin
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Apr 18, 2008·The Journal of Pharmacy and Pharmacology·Takayuki SeoKazuko Nakagawa

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Datasets Mentioned

BETA
AC022335
AB026257

Methods Mentioned

BETA
genotyping
PCR

Software Mentioned

Pyrosequencing
EMLD
Oligo primer
AGOWA
BiAS
SNP Primer Design
PHASE

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