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.

<b><i>研究背景：</i></b> 药物反应的个体间遗传差异可导致治疗失败或药物不良反应（ADRs）。本研究旨在依据常用处方药的既定给药指南，评估葡萄牙南部人群的药物基因组学特征，并将其与已完成基因分型的人群进行对比。<b><i>研究方法：</i></b> 本研究依托欧洲健康检查调查（EHES）葡萄牙分支项目开展，为横断面研究。共对208名受试者的23个基因中的47个药物基因组学相关变异位点进行了基因分型。计算等位基因频率与基因型频率，明确受试者的药物基因组学特征。通过电子数据库检索开展对比分析，并进行两两Fst计算以评估人群间的遗传距离。<b><i>研究结果：</i></b> 本研究发现，葡萄牙区域人群在CYP2C9 rs1057910、CYP2D6 rs3892097、MTHFR rs1801133及F5 rs6025位点上存在显著的轻度遗传分化。当纳入4个国际人类基因组单体型图计划（HapMap）人群进行分析时，ADH1B rs2066702、ADH1B rs1229984、NAT2 rs1799931及VKORC1 rs9923231位点呈现出显著的人群遗传分化。本研究发现，18.9%的受试者同时为至少3种药物的中间代谢型或弱代谢型，且84.6%的受试者携带至少1种与所研究药物相关的治疗失败或ADR风险等位基因。<b><i>研究结论：</i></b> 针对葡萄牙南部人群广泛使用的药物，与其代谢改变相关的风险等位基因携带率较高。该研究结果有助于预测药物临床疗效与/或毒性，优化治疗响应并提升成本效益比。