PharmVar Standardises SLCO1B1 Star Allele Nomenclature for Statin Safety Testing
This PharmVar GeneFocus establishes standardised star allele nomenclature for SLCO1B1, the gene encoding the OATP1B1 drug transporter critical for hepatic statin uptake. SLCO1B1 variants are strongly associated with statin-associated musculoskeletal symptoms, and this nomenclature has been adopted by the 2022 CPIC statin guideline. For clinical laboratories, consistent SLCO1B1 reporting is essential as preemptive pharmacogenomic panels increasingly include this transporter gene.
The original study
PharmVar GeneFocus: SLCO1B1.
- Authors
- Ramsey LB, Gong L, Lee SB, Wagner JB, Zhou X, Sangkuhl K, et al.
- Journal
- Clinical pharmacology and therapeutics
- Type
- Journal Article, Review, Research Support, N.I.H., Extramural
- PMID
- 35797228
Original 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.