Background/Objectives: Statins are the first-line lipid-lowering therapy, but their use is limited by interindividual variability in efficacy and safety, particularly statin-associated muscle symptoms. This systematic review aimed to identify pharmacogenetic biomarkers related to statin response, compare them with regulatory recommendations, and propose a candidate pharmacogenetic panel for future clinical validation and implementation studies. Methods: A PRISMA-based systematic review identified 78 eligible studies. A novel composite consistency index integrated the frequency and direction of reported associations across studies, weighted by the methodological quality of the evidence. Identified pharmacogenetic biomarkers were compared with international pharmacogenetic guidelines and Spanish regulatory recommendations to support prioritization. Results:SLCO1B1 showed the strongest and most consistent evidence, particularly for simvastatin-induced myotoxicity, whereas ABCG2 demonstrated the most consistent evidence for rosuvastatin. Evidence linking genetic biomarkers to atorvastatin-related adverse reactions was heterogeneous, while CYP2C9 was associated with fluvastatin response. Other biomarkers were positively associated with statin-related adverse reactions; however, the available evidence remains limited. Conclusions: International guidelines and Spanish regulatory resources revealed substantial concordance despite differences in biomarker inclusion and therapeutic recommendations. Based on the available evidence, a candidate pharmacogenetic biomarker panel is proposed for future implementation studies in personalized statin therapy. SLCO1B1 and ABCG2 emerged as the biomarkers with the strongest and most consistent support across published evidence, regulatory recommendations, and established statin transport pathways. CYP2C9 was also identified as a potentially relevant implementation biomarker; however, the supporting evidence was more limited. Additional biomarkers showed positive associations with statin-related adverse reactions; however, further validation is required.

Background: Interindividual variability in sertraline pharmacokinetics remains substantial, but the relative contributions of pharmacogenetic (PGx), demographic, clinical, and prescribing determinants have not been comprehensively evaluated in routine clinical practice. The study aimed to evaluate PGx, demographic, clinical, and prescribing determinants of sertraline plasma concentrations, sertraline plasma concentration-to-dose ratio (C/D), and non-dose-normalized sertraline-to-norsertraline metabolic ratio (MR), with log₁₀-transformed dose-normalized sertraline/norsertraline metabolic ratio (LogMR_DN) and log₁₀-transformed MR (LogMR) evaluated as exploratory derived pharmacokinetic outcomes in real-world clinical settings. Methods: This prospective real-world PGx study included 153 patients receiving sertraline therapy who participated in the MedeA clinical PGx implementation program. Associations of genotype-predicted phenotypes for CYP2C19, CYP2B6, CYP2D6, CYP2C9, and CYP3A4, CYP2C:TG haplotype status, demographic, clinical, and prescribing characteristics with sertraline concentration, C/D, MR, and LogMR_DN were evaluated using univariable analyses. Separate multivariable linear regression models were fitted for these outcomes and LogMR using 140 complete cases. Results: CYP2C19 gPM status was associated with higher sertraline concentrations (β = 72.10, 95% CI: 21.36–122.84; p = 0.01). Although a higher sertraline C/D ratio was observed in the conventional multivariable model with CYP2C19 gPM (β = 1.46, 95% CI: 0.85–2.08; p < 0.001), this association was not retained after HC3 heteroscedasticity-robust standard errors were applied (β = 1.46, 95% CI: −0.09–3.02; p = 0.07). In a small exploratory subgroup analysis, patients with combined CYP2C19 and CYP2B6 poor-metabolizer status (n = 2) had sertraline concentrations exceeding 150 ng/mL. Conclusions: The study findings provide further insights into the relevance of CYP2C19 in sertraline pharmacokinetics.