Acosta-Monterrosa Andy A, Montoya-Quintero Kevin Fernando, Galván-Barrios Johana, Rojas Torres Indiana Luz
Faculty of Exact and Natural Sciences, Universidad de Cartagena, Cartagena, Colombia.
Center for Meta-Research and Scientometrics in Biomedical Sciences, Barranquilla, Colombia.
Front Pharmacol. 2025 Aug 29;16:1636451. doi: 10.3389/fphar.2025.1636451. eCollection 2025.
To generate an ancestry-resolved pharmacogenomic (PGx) landscape for Colombia by integrating all PharmGKB variant-drug annotations with local allele-frequency data, thereby quantifying inter-ancestry differences of clinical relevance and exposing evidence gaps that hinder equitable precision medicine.
We conducted a cross-sectional analysis of 4,462 PharmGKB variant annotations (1994-2024), retaining 1,216 significant single-nucleotide polymorphisms (SNPs) reported in 552 studies. Allele frequencies were extracted for five Colombian populations: two predominantly African (Palenque [PLQ], Chocó [CHG]) and three predominantly European (ATQCES, ATQPGC, CLM), from the CÓDIGO database. Spearman correlations compared population-specific PGx profiles; SNPs with >25 percentage-point frequency differentials were tabulated.
European ancestry dominated the global evidence base, representing 51.5% of 651,532 participants, while African ancestry accounted for only 0.46% (n = 3,031). Strong correlations were observed among European-leaning Antioquians ( ≥ 0.90), whereas PLQ exhibited inverse or negligible correlations with those groups ( = -0.20 to -0.02) and minimal similarity with CHG ( = 0.12). Twenty-eight SNPs were frequent in PLQ (>75%) but rare in Europeans (<50%), and 44 showed the opposite pattern. Notable examples include CYP3A4 rs3735451-C (rivaroxaban; 87.1% vs. 23.2%), CYP3A5 rs776746-T (tacrolimus; 85% vs. 23.5%), and rs55881666-C (duloxetine; 15% vs. 84%). Globally, 71.5% of PGx studies originated in high-income countries.
Large, clinically actionable allele-frequency contrasts and pronounced discovery biases confirm the need for ancestry-aware PGx testing and locally calibrated dosing algorithms in Colombia. The analytic framework and variant catalogue generated knowledge to operationalize precision pharmacotherapy across admixed Latin-American populations.
通过整合所有PharmGKB变异-药物注释与当地等位基因频率数据，生成哥伦比亚的祖先解析药物基因组学（PGx）图谱，从而量化具有临床相关性的祖先间差异，并揭示阻碍公平精准医学的证据差距。
我们对4462个PharmGKB变异注释（1994 - 2024年）进行了横断面分析，保留了552项研究中报告的1216个显著单核苷酸多态性（SNP）。从CÓDIGO数据库中提取了五个哥伦比亚人群的等位基因频率：两个主要为非洲裔（帕伦克[PLQ]、乔科[CHG]）和三个主要为欧洲裔（ATQCES、ATQPGC、CLM）。使用斯皮尔曼相关性比较特定人群的PGx谱；列出频率差异超过25个百分点的SNP。
欧洲血统在全球证据基础中占主导地位，在651532名参与者中占51.5%，而非洲血统仅占0.46%（n = 3031）。在倾向欧洲的安蒂奥基亚人中观察到强相关性（≥0.90），而PLQ与这些群体表现出负相关或可忽略不计的相关性（= -0.20至 -0.02），与CHG的相似性最小（= 0.12）。28个SNP在PLQ中频率较高（>75%）但在欧洲人中频率较低（<50%），44个SNP呈现相反模式。显著的例子包括CYP3A4 rs3735451 - C（利伐沙班；87.1%对23.2%）、CYP3A5 rs776746 - T（他克莫司；85%对23.5%）和rs55881666 - C（度洛西汀；15%对84%）。在全球范围内，71.5%的PGx研究起源于高收入国家。
巨大的、具有临床可操作性的等位基因频率差异和明显的发现偏差证实了在哥伦比亚需要进行考虑祖先的PGx检测和本地校准的给药算法。所生成的分析框架和变异目录为在混合的拉丁裔人群中实施精准药物治疗提供了知识。
