Genes, Vol. 15, Pages 99: SLCO1B1 Genetic Variation Influence on Atorvastatin Systemic Exposure in Pediatric Hypercholesterolemia

Genes, Vol. 15, Pages 99: SLCO1B1 Genetic Variation Influence on Atorvastatin Systemic Exposure in Pediatric Hypercholesterolemia Genes doi: 10.3390/genes15010099 Authors: Jonathan B. Wagner Susan Abdel-Rahman Geetha Raghuveer Andrea Gaedigk Erin C. Boone Roger Gaedigk Vincent S. Staggs Gregory A. Reed Na Zhang J. Steven Leeder This clinical study examined the influence of SLCO1B1 c.521T>C (rs4149056) on plasma atorvastatin concentrations in pediatric hypercholesterolemia. The participants (8–21 years), including heterozygous (c.521T/C, n = 13), homozygous (c.521C/C, n = 2) and controls (c.521T/T, n = 13), completed a single-oral-dose pharmacokinetic study. Similar to in adults, the atorvastatin (AVA) area-under-concentration-time curve from 0 to 24 h (AUC0–24) was 1.7-fold and 2.8-fold higher in participants with c.521T/C and c.521C/C compared to the c.521T/T participants, respectively. The inter-individual variability in AVA exposure within these genotype groups ranged from 2.3 to 4.8-fold, indicating that additional factors contribute to the inter-individual variability in the AVA dose–exposure relationship. A multivariate model reinforced the SLCO1B1 c.521T>C variant as the central factor contributing to AVA systemic exposure in this pediatric cohort, accounting for ~65% of the variability in AVA AUC0–24. Furthermore, lower AVA lactone concentrations in participants wit...
Source: Genes - Category: Genetics & Stem Cells Authors: Tags: Article Source Type: research