Supplementary Material for: Pharmacogenetic Profile of a South Portuguese Population: Results from the Pilot Study of the European Health Examination Survey in Portugal

<b><i>Background:</i></b> The genetic inter-individual variability of drug response can lead to therapeutic failure or adverse drug reactions (ADRs). The aims of this study were to assess the pharmacogenetic profile of a South Portuguese population according to established dosing guidelines for commonly prescribed drugs and to compare it with that of previously genotyped populations. <b><i>Methods:</i></b> A cross-sectional study was developed in the context of the Portuguese Component of the European Health Examination Survey (EHES). A total of 47 pharmacogenetically relevant variants in 23 different genes were genotyped in 208 participants. Allelic and genotypic frequencies were calculated, and the pharmacogenetic profile of the participants was defined. A comparative analysis was conducted through electronic database search. Pairwise<i> Fst</i> calculations were performed to assess the genetic distance between populations. <b><i>Results:</i></b> We found a significant small differentiation between the Portuguese regional populations regarding <i>CYP2C9 </i>rs1057910<i>, CYP2D6 </i>rs3892097<i>, MTHFR </i>rs1801133 and <i>F5 </i>rs6025. When consid-ering 4 HapMap populations, <i>ADH1B</i> rs2066702,<i> ADH1B</i> rs1229984,<i> NAT2</i> rs1799931 and <i>VKORC1</i> rs9923231 displayed a significant population differentiation. We found that 18.9% of the participants are intermediate or poor metabolizers for at least 3 drugs simultaneously and that 84.6% of the participants have at least one therapeutic failure or ADR risk allele for the considered drugs. <b><i>Conclusions:</i></b> There is a high prevalence of risk alleles associated with an altered drug metabolism regarding drugs largely used by the South Portuguese population. This knowledge contributes to the prediction of their clinical efficacy and/or toxicity, optimizing therapeutic response while improving cost-effectiveness.