SLCO1B1 Functional Variants, Bilirubin, Statin-Induced Myotoxicity, and Recent Sub-Saharan African Ancestry: A Precision Medicine Health Equity Study.

• Tác giả: Willow Coyote-Maetas, Michael P Douglas, Tanushree Haldar, Carlos Iribarren, Linda Kachuri, Ronald M Krauss, Mark Kvale, Marisa W Medina, Akinyemi Oni-Orisan, John S Witte, Jia Yang, Sook Wah Yee
• Ngôn ngữ: eng
• Ký hiệu phân loại: 515.9 Functions of complex variables
• Thông tin xuất bản: United States : Clinical pharmacology and therapeutics , 2025
• Bộ sưu tập: NCBI
• ID: 753729

Tóm tắt

Statin pharmacogenetic implementation guidelines are derived from evidence of primarily Eurocentrically biased study populations. Functional SLCO1B1 variants that are rare in these study populations have not been equitably investigated and are thus missing from guidelines. The objective of this precision medicine health equity study was to determine the clinical validity of understudied candidate functional SLCO1B1 variants common in people with 1,000 Genomes sub-Saharan African superpopulation (1KG-AFR-like) genetic similarity. We conducted our analyses using the real-world evidence of participants from three large, electronic health record-linked biobanks. We used bilirubin levels (as an endogenous substrate of organic anion transporting polypeptide [OATP1B1] function) and severe statin-induced myotoxicity phenotypes. Loss-of-function splice variant rs77271279 (P = 1.1 × 10