Chora, Joana RitaGrade, M. M.Antunes, M.Bourbon, M.2026-03-042026-03-042025-11-05http://hdl.handle.net/10400.18/11115((Final programme: https://www.esptcongress.org/wp-content/uploads/2025/10/FINAL-Programme.pdf))Background/Aims: Genetic variants in pharmacogenes involved in statin transport, metabolism, and excretion can increase the risk of adverse effects, particularly statin-associated musculoskeletal symptoms (SAMS). Loss-of-function haplotypes in SLCO1B1 are reliably linked to elevated SAMS risk. Familial hypercholesterolemia (FH), a high cardiovascular disease risk condition, requires lifelong lipid-lowering therapy, often from a young age. However, studies of statin pharmacogenomics in FH patients remain scarce. The Portuguese population, shaped by millennia of admixture, displays a complex genetic background with potential implications for pharmacogenomic diversity. This study aimed to assess the prevalence of high-risk alleles in genes related to statin metabolism and transport, including variants relevant to therapeutic efficacy, in both the general Portuguese population and FH patients. Methods: We analysed 738 adults from the nationally representative e_Cor cohort and 489 clinical FH patients. Genotyping of 13 statin-related single-nucleotide variants (SNV) was conducted using both OpenArrayTM technology and NGS target sequencing. Statin-medicated individuals from both cohorts (N=903) were further analysed for pharmacogenomic risk. Results: Compared to public databases, the frequency of the APOE rs429358 risk allele was significantly lower in the general Portuguese cohort, but significantly higher in statin-medicated individuals and FH patients. Genotype distributions of SLCO1B1, ABCB1, HMGCR, and MTHFR SNVs differed significantly between medicated individuals from the general population and FH patients. Among all participants, 2% had SLCO1B1 poor-function and 22% decreased-function haplotypes; these frequencies were slightly higher in the medicated group (3% and 23%, respectively). Notably, 40% of poor-function and 32% of decreased-function carriers were prescribed a statin dose/type considered high-risk for SAMS. Differences between FH-positive and negative individuals were only observed for APOE rs429358. Conclusion: This study presents a comprehensive overview of statin-related pharmacogenetic variation in the Portuguese population and FH patients. The high prevalence of actionable variants underlines the importance of pharmacogenomic-informed prescribing in high-risk groups. Integrating genetic information into clinical decision-making can optimise statin therapy, mitigate adverse effects, and enhance the effectiveness of personalised lipid-lowering strategies in Portugal.engStatinsPharmacogenomicsFamilial HypercholesterolemiaPortugalDoenças Cardio e Cérebro-vascularesconference object