Publicação
Pharmacogenomic Risk Profiling of Statin Response in Portuguese Familial Hypercholesterolemia and General Population Cohorts
| datacite.subject.fos | Ciências Médicas | |
| dc.contributor.author | Chora, Joana Rita | |
| dc.contributor.author | Grade, M. M. | |
| dc.contributor.author | Antunes, M. | |
| dc.contributor.author | Bourbon, M. | |
| dc.date.accessioned | 2026-03-04T13:02:03Z | |
| dc.date.available | 2026-03-04T13:02:03Z | |
| dc.date.issued | 2025-11-05 | |
| dc.description | ((Final programme: https://www.esptcongress.org/wp-content/uploads/2025/10/FINAL-Programme.pdf)) | |
| dc.description.abstract | 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. | eng |
| dc.identifier.uri | http://hdl.handle.net/10400.18/11115 | |
| dc.language.iso | eng | |
| dc.peerreviewed | n/a | |
| dc.rights.uri | N/A | |
| dc.subject | Statins | |
| dc.subject | Pharmacogenomics | |
| dc.subject | Familial Hypercholesterolemia | |
| dc.subject | Portugal | |
| dc.subject | Doenças Cardio e Cérebro-vasculares | |
| dc.title | Pharmacogenomic Risk Profiling of Statin Response in Portuguese Familial Hypercholesterolemia and General Population Cohorts | eng |
| dc.type | conference object | |
| dspace.entity.type | Publication | |
| oaire.citation.conferenceDate | 2025-11 | |
| oaire.citation.conferencePlace | Rotterdam, Netherlands | |
| oaire.citation.title | 8th International Congress of the European Society for Pharmacogenomics and Personalised Therapy (ESPT), 5-8 November 2025 | |
| oaire.version | http://purl.org/coar/version/c_b1a7d7d4d402bcce |