Year: 2026
Type: editorial
Abstract: The Research Topic "Innovations in PGx: embracing diversity and clinical application" was launched to highlight studies that address these challenges by focusing on clinical translation, implementation in routine settings, ancestry-aware approaches, and emerging biomarkers or analytical strategies. The eleven articles included in this collection reflect the breadth of contemporary PGx, spanning commonly prescribed medicines, high-risk clinical contexts, multiethnic cohorts, and expanding molecular determinants of drug response.Several contributions revisit established pharmacogenes and widely used therapies, emphasizing the importance of consolidating and clarifying evidence for clinical use. Ibrahim et al. 1 review the relationship between CYP2C19 polymorphisms and adverse drug reactions associated with proton pump inhibitors (PPIs). While PPIs are frequently prescribed and generally well tolerated, concerns persist regarding long-term adverse effects. The review highlights heterogeneity across observational studies and notes that existing findings are often conflicting or modest, underscoring the need for appropriately designed studies that can better address confounding and long-term outcomes.Clinical translation is more directly addressed by Mohammed et al. 2 , who conducted a systematic review and meta-analysis evaluating point-of-care CYP2C19 genotyping to guide P2Y12 inhibitor selection in patients undergoing percutaneous coronary intervention. Across randomized controlled trials, genotype-guided antiplatelet therapy was associated with reduced recurrent myocardial infarction and a lower risk of composite major adverse cardiovascular events. These findings support the role of rapid genotyping in time-sensitive settings where treatment decisions must be made promptly.Implementation science and service design are represented by Alghamdi et al. 3 , who describe the integration of a multidisciplinary PGx service into an underserved integrated behavioral health clinic in the United States. Surveyed clinicians reported high perceived potential benefit alongside concerns related to cost, clinical utility, and workflow disruption, and expressed interest in PGx-focused training. The described pharmacist-driven model and the use of preemptive and reactive testing pathways offer a pragmatic example of how PGx services may be integrated into routine care in settings where resources and access constraints are prominent.In specialized clinical settings, evidence synthesis remains essential to identify actionable signals and define research gaps. The systematic review by Da Costa-Junior et al 4 . on CYP3A5, CYP3A4, and ABCB1 polymorphisms in hematopoietic cell transplantation recipients summarizes observational data on tacrolimus and cyclosporine outcomes. The review reports that the presence of the CYP3A5*3 allele influences tacrolimus exposure and related measures, while the evidence for CYP3A4 and ABCB1 is more limited.Besides clinical implementation challenges, a core focus of this Research Topic is genetic diversity and the clinical implications of population variation. Biswas et al. 5 estimate the prevalence of the risk alleles CYP2C9 (*2, *3) and VKORC1 c.-1639G>A across global populations using 1000 Genomes data, and map these to PGx-guideline-relevant phenotypes. The analyses show substantial differences across ancestry groups, illustrating how a "one-size-fits-all" approach to dosing may disproportionately affect specific populations.The interface between pharmacogenetics, drug safety, and regulation is examined by Santos Fidelis et al. 6 in a systematic review of genetic variants associated with metamizole-induced agranulocytosis. The authors summarize the limited available evidence across a small number of studies, with reported signals including HLA-C*04:01 and multiple variants on chromosome nine. By integrating allele frequency data from diverse ancestry groups and a global review of regulatory status, the study highlights the current constraints of the evidence base and argues for larger, well-characterized investigations before genetic findings can reasonably inform regulatory differences across settings.Real-world evidence from a multiethnic cohort is provided by Alqasrawi et al. 7 , who evaluated pharmacogenomic predictors of rosuvastatin discontinuation in the United Arab Emirates. In this prospective observational study, the ABCG2 rs2231142 variant was associated with an increased discontinuation risk, whereas SLCO1B1 rs4149056 was not associated with discontinuation in this setting. By linking genetic variability to treatment persistence and LDL-cholesterol change in routine care, this work illustrates how PGx can inform tolerability and adherence considerations in diverse populations.Acosta-Monterrosa et al 8 . extend the diversity lens by integrating PharmGKB variant-drug annotations with local allele-frequency data to generate an ancestry-resolved PGx landscape for Colombia. The study quantifies substantial inter-population differences. In particular between African-leaning and European-leaning groups, thereby highlighting the imbalance of global PGx evidence toward European ancestry. Beyond documenting disparities, the authors provide an analytic framework and catalog that can support locally informed prioritization of variants and calibration of precision pharmacotherapy approaches in admixed populations.The clinical utility of PGx in pediatrics is addressed by Maggo et al. 9 , who extracted PGx-relevant information from clinical exome sequencing in a racially diverse cohort of children. The majority of patients carried at least one actionable PGx phenotype across evaluated pharmacogenes. Phenotype frequencies clearly varied based on patients ancestry, highlighting the importance of ancestry awareness.This topic also includes work pointing to emerging biomarkers and mechanistic hypotheses beyond classical pharmacogenes. Abou Warda et al 10 . evaluated associations between SLC5A2 variation and outcomes in heart failure cohorts, including a dapagliflozin-treated population. The observed genotypeoutcome patterns differed by treatment status, suggesting that SLC5A2 variants may be informative for understanding heterogeneity in clinical trajectories and treatment response, while warranting replication and mechanistic follow-up.Finally, Xu et al. 11 review progress on N6-methyladenosine (m6A) RNA modifications and drug resistance in gastrointestinal tumors, summarizing how "writers," "erasers," and "readers" may influence RNA processing and downstream pathways relevant to chemotherapy, targeted agents, and immunotherapy. They explore the biological function and resistance mechanisms of m6A to synthesize new ideas and targets for future treatment.In summary, the articles in this Research Topic underscore important developments in pharmacogenomics: generating clinically useful evidence in real-world contexts and ensuring that PGx knowledge is applicable across diverse populations. Collectively, they support continued efforts toward inclusive study designs, implementation-ready pathways, and the integration of emerging biomarkers to advance precision medicine.
Source: Frontiers in Pharmacology
Language: English
Subfield: Pharmacology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7128780452
Cites:
Cited by:
Related to: