Direct and Rapid Genotyping of SLCO1B1 388A>G and 521T>C in Human Blood Specimens Using the SmartAmp-2 Method

Abstract

Abstract. Organic anion-transporting polypeptide (OATP) 1B1, encoded by the solute carrier organic anion transporter family member 1B1 (SLCO1B1) gene, mediates the active uptake of various organic anions into hepatocytes and determines their hepatic clearances as the first step in the detoxification pathway. Previous reports indicated that alterations in its function by drug-drug interactions or genetic polymorphisms affect the pharmacokinetics of the substrate drugs. In the present study, we developed a method to genotype SLCO1B1 388A>G (rs2306283) and 521>C (rs4149056), which significantly affect the clinical pharmacokinetics and subsequent side effects such as myopathy caused by statins, OATP1B1 substrates in humans. We used a small aliquot of blood and the isothermal Smart Amplification Process version 2 (SmartAmp-2), which could complete the genotyping of 388A>G and 521T>C within 60 min. The genotypes of 101 genomic DNA samples and blood samples assessed by SmartAmp-2 matched perfectly to those determined previously by the conventional PCR-SSCP method. The SmartAmp-2 method enables the rapid identification of the 388A>G and 521T>C genotypes, saving time and effort in the genomic DNA preparation in clinical practice. This method will be useful for evaluating and predicting altered pharmacological and toxicological effects of substrate drugs caused by SLCO1B1 polymorphisms.

Role of SLCO1B1, ABCB1, and CHRNA1 gene polymorphisms on the efficacy of rocuronium in Chinese patients

“…Yoshida et al reported quaternary ammonium salt muscle relaxants transited from blood to liver cells mainly through the organic anion transporters. Organic anion‐transporting polypeptide (OATP) 1B1, which is encoded by the solute carrier organic anion transporter family member 1B1 (SLCO1B1) gene, mediates the active uptake of various organic anions into hepatocytes and determines their hepatic clearance as the first step in the detoxification pathway . Previous reports indicated that alterations in function by drug‐drug interactions or genetic polymorphisms affected the pharmacokinetics of the drugs.…”

“…Rocuronium belongs to single quaternary ammonium muscle relaxant. Yoshida et al reported 1,19 quaternary ammonium salt muscle relaxants transited from blood to liver cells mainly through the organic anion transporters. OATP 1B1, which is encoded by the solute carrier organic anion transporter family member 1B1 (SLCO1B1) gene, mediates the active uptake of various organic anions into hepatocytes and determines their hepatic clearances as the first step in the detoxification pathway.…”

“…OATP 1B1, which is encoded by the solute carrier organic anion transporter family member 1B1 (SLCO1B1) gene, mediates the active uptake of various organic anions into hepatocytes and determines their hepatic clearances as the first step in the detoxification pathway. 19 Previous reports 20,21 indicated that alterations in its function by drug-drug interactions or genetic polymorphisms affected the pharmacokinetics of the drugs. Müller and Fromm reported that SLCO1B1 gene variant can have an impact on drug metabolism, such as digoxin and metformin.…”

Influence of 6 genetic variants on the efficacy of statins in patients with dyslipidemia

“…SLCO1B1 codes for a transport protein essential for the entry of statins to the hepatocytes. The variant c.521T > C produces a loss of activity of the protein and it is known to be related to the development of secondary effects of statin treatment . CYP3A4 codes for an isoform of P450 cytochrome, and it is involved in the initial metabolism of statins, reducing their bioavailability.…”

“…The variant c.521T > C produces a loss of activity of the protein and it is known to be related to the development of secondary effects of statin treatment. [15][16][17] codes for an isoform of P450 cytochrome, and it is involved in the initial metabolism of statins, reducing their bioavailability. The variant (c.-392G > A) inhibits the binding of a repressor to the promoter, so there is an over-expression of the protein and a greater degradation of the drug.…”