Gil-Rodriguez Almudena, Recarey-Rama Sheila, Rodríguez-Viyuela Ana, Cruz Raquel, Barros Francisco, Carracedo Angel, Maroñas Olalla
Pharmacogenomics and Drug Discovery (GenDeM) Group, Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain.
Genomic Medicine Group, CIMUS, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain.
Pharmaceuticals (Basel). 2025 Apr 1;18(4):515. doi: 10.3390/ph18040515.
: Fluoropyrimidine derivatives, 5-fluorouracil (5-FU) and its prodrugs (capecitabine and tegafur), are widely used in patients suffering from colorectal cancer. The enzyme responsible for their metabolization, dihydropyrimidine dehydrogenase (DPD), is encoded by the gene, which is highly polymorphic and may contain polymorphisms which could severely compromise its function. This article aims to describe the prevalence of the four main polymorphisms in the Galician population (Spain) and to compare these frequencies with data obtained from European cohorts in genetic databases and a Spanish study. : Galician data frequencies for the four main polymorphisms recommended by the European Medicine Agency (EMA) and the Spanish Agency for Medicines and Health Products (AEMPS) (rs3918290 (c.1905+1G>A), rs55886062 (c.1679T>G), rs56038477 (c.1236G>A) and rs67376798 (c.2846A>T)) were collected, as well as data from the genomic databases 1000 Genomes and gnomAD. Additionally, the results from a Spanish study were included. : Significant differences in variant allele frequencies were observed in the Galician population compared to the frequencies reported in the European population, as well as in the Spanish PhotoDPYD study. Specifically, the rs56038477-T variant (most prevalent) along with the rs3918290-T variant, exhibited significantly lower frequencies than anticipated in the Galician cohort, with a high degree of statistical significance. : Observed allele frequencies for the four variants suggest that Europeans and Spanish frequencies may not be fully applicable to the Galician population. These results emphasize the emerging need for incorporating the genetic information of populations that might be underrepresented into populational databases available worldwide.
氟嘧啶衍生物，5-氟尿嘧啶（5-FU）及其前体药物（卡培他滨和替加氟），被广泛应用于结直肠癌患者。负责其代谢的酶，二氢嘧啶脱氢酶（DPD），由该基因编码，该基因具有高度多态性，可能包含严重损害其功能的多态性。本文旨在描述加利西亚人群（西班牙）中四种主要多态性的患病率，并将这些频率与从欧洲队列的遗传数据库和一项西班牙研究中获得的数据进行比较。收集了欧洲药品管理局（EMA）和西班牙药品与健康产品管理局（AEMPS）推荐的四种主要多态性（rs3918290（c.1905+1G>A）、rs55886062（c.1679T>G）、rs56038477（c.1236G>A）和rs67376798（c.2846A>T））在加利西亚人群中的数据频率，以及来自基因组数据库千人基因组计划和gnomAD的数据。此外，还纳入了一项西班牙研究的结果。与欧洲人群以及西班牙PhotoDPYD研究报告的频率相比，在加利西亚人群中观察到变异等位基因频率存在显著差异。具体而言，rs56038477-T变异（最常见）以及rs3918290-T变异，在加利西亚队列中的频率显著低于预期，具有高度统计学意义。观察到的四种变异的等位基因频率表明，欧洲人和西班牙人的频率可能不完全适用于加利西亚人群。这些结果强调了将可能代表性不足的人群的遗传信息纳入全球可用的人群数据库的迫切需求。
