PharmVar GeneFocus: SLCO1B1.

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Abstract

The Pharmacogene Variation Consortium (PharmVar) is now providing star (*) allele nomenclature for the highly polymorphic human SLCO1B1 gene encoding the organic anion transporting polypeptide 1B1 (OATP1B1) drug transporter. Genetic variation within the SLCO1B1 gene locus impacts drug transport, which can lead to altered pharmacokinetic profiles of several commonly prescribed drugs. Variable OATP1B1 function is of particular importance regarding hepatic uptake of statins and the risk of statin-associated musculoskeletal symptoms. To introduce this important drug transporter gene into the PharmVar database and serve as a unified reference of haplotype variation moving forward, an international group of gene experts has performed an extensive review of all published SLCO1B1 star alleles. Previously published star alleles were self-assigned by authors and only loosely followed the star nomenclature system that was first developed for cytochrome P450 genes. This nomenclature system has been standardized by PharmVar and is now applied to other important pharmacogenes such as SLCO1B1. In addition, data from the 1000 Genomes Project and investigator-submitted data were utilized to confirm existing haplotypes, fill knowledge gaps, and/or define novel star alleles. The PharmVar-developed SLCO1B1 nomenclature has been incorporated by the Clinical Pharmacogenetics Implementation Consortium (CPIC) 2022 guideline on statin-associated musculoskeletal symptoms.

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Journal

Journal ID (iso-abbrev): Clin Pharmacol Ther

Title: Clinical pharmacology and therapeutics

Publisher: Wiley

ISSN (Electronic): 1532-6535

ISSN (Print): 0009-9236

Publication date (Electronic): Apr 2023

Volume: 113

Issue: 4

Affiliations

[1 ] Divisions of Clinical Pharmacology and Research in Patient Services, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.

[2 ] Department of Biomedical Data Science, Stanford University, Stanford, California, USA.

[3 ] Precision Medicine Institute, Macrogen Inc., Seoul, Korea.

[4 ] Division of Clinical Pharmacology, Toxicology & Therapeutic Innovation, Children's Mercy Kansas City, Kansas City, Missouri, USA.

[5 ] School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri, USA.

[6 ] Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California, USA.

[7 ] School of Pharmacy, Shenandoah University, Fairfax, Virginia, USA.

[8 ] Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA.

[9 ] School of Pharmacy and Institute for Precision Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

[10 ] Department of Medicine (BMIR), Stanford University, Stanford, California, USA.

[11 ] Department of Clinical Pharmacology, University of Helsinki, Helsinki, Finland.

[12 ] Individualized Drug Therapy Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

[13 ] Department of Clinical Pharmacology, HUS Diagnostic Center, Helsinki University Hospital, Helsinki, Finland.

Article

DOI: 10.1002/cpt.2705

PubMed ID: 35797228

SO-VID: fded3be7-ff5e-4b49-b02b-cec8a6b542f6

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