Aust Prescr. 2025 Jun;48(3):82-86. doi: 10.18773/austprescr.2025.021.

ABSTRACT

Pharmacogenomic testing provides information on whether a patient possesses gene variants that can influence drug exposure or response. It can be used as part of clinical decision-making to personalise drug therapy. Pharmacogenomic testing can help identify patients at higher risk of serious adverse drug reactions or therapeutic failure, and sometimes it can explain unexpected adverse effects or poor efficacy in patients already on drug therapy. As drug responses are influenced by many factors, pharmacogenomic test results must always be interpreted in the clinical context of the patient. At the time of writing, tests for thiopurine methyltransferase (TPMT) (azathioprine, mercaptopurine, thioguanine) and human leucocyte antigen B*57:01 (abacavir) are Medicare-rebated. Pharmacogenomic testing is also recommended for several other drugs, such as allopurinol and clopidogrel, but these do not currently attract a Medicare rebate.

PMID:40568692 | PMC:PMC12187479 | DOI:10.18773/austprescr.2025.021

bioRxiv [Preprint]. 2025 May 1:2025.04.28.651081. doi: 10.1101/2025.04.28.651081.

ABSTRACT

The Consortium for Genomic Diversity, Ancestry, and Health in Colombia (CÓDIGO) aims to build a community of Colombian researchers in support of local capacity in genomics, bioinformatics, and precision health. Here, we present the first CÓDIGO data release and the consortium web platform, including annotations for more than 95 million genetic variants from 1,441 samples representing 14 populations from across the country. CÓDIGO samples show a wide range of African (16.7%), European (50.6%), and Indigenous American (32.8%) genetic ancestry components, with five distinct ancestry clusters. Thousands of ancestry-enriched variants, with divergent allele frequencies across clusters, show pharmacogenomic and clinical genetic associations. Examples include African ancestry-enriched variants associated with fast metabolism of the immunosuppressive drug tacrolimus and malaria resistance and European ancestry-enriched variants associated with nicotine dependence and hereditary hemochromatosis. CÓDIGO reveals the nexus between ancestry and health in Colombia and underscores the utility of collaborative genome sequence analysis efforts.

PMID:40568136 | PMC:PMC12190313 | DOI:10.1101/2025.04.28.651081

Front Oncol. 2025 Jun 11;15:1590128. doi: 10.3389/fonc.2025.1590128. eCollection 2025.

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) is a major cause of global cancer deaths, with increasing incidence among younger populations. Despite advancements in diagnostic and therapeutic strategies, early detection and effective treatment remain major challenges. Exosomes act as critical intercellular messengers, promoting cancer growth, immune escape, and chemotherapy resistance. This study aims to identify exosome-related biomarkers in CRC and elucidate the functional significance of S100A11 in tumor progression and immune regulation.

METHODS: We integrated multi-cohort transcriptomic data from TCGA and GEO databases and applied a machine learning triad (LASSO-SVM-Random Forest) to identify robust exosomal biomarkers for CRC. Functional enrichment analysis, immune infiltration evaluation, and molecular docking were performed, along with in vitro and in vivo experiments, including qPCR, Western blot, IHC, apoptosis assays, and xenograft models, were performed to validate the oncogenic and immunoregulatory role of S100A11.

RESULTS: A five-gene exosome-based diagnostic panel (S100A11, CA4, PDCD4, GSTM2, SORD) was established, demonstrating excellent predictive accuracy (AUC=0.965). S100A11 was identified as a master regulator of CRC proliferation, immune modulation, and chemoresistance. Knockdown of S100A11 significantly suppressed CRC cell proliferation, induced apoptosis, and restrained tumor development in a xenograft model. Moreover, S100A11 was associated with an immunosuppressive tumor microenvironment. Pharmacogenomic analysis revealed its potential as a therapeutic target, with high binding affinity to diallyl trisulfide, suggesting novel treatment avenues.

CONCLUSION: S100A11 mechanistically promotes CRC progression by activating oncogenic signaling and reshaping the immune microenvironment, positioning it as a clinically relevant dual-function biomarker. The integration of bioinformatics, machine learning, and experimental validation underscores the potential of exosome-derived markers for immunotherapy and precision oncology. Future studies should focus on clinical validation and the development of exosome-based immune-targeted therapies for CRC management.

PMID:40567612 | PMC:PMC12187594 | DOI:10.3389/fonc.2025.1590128

J Can Assoc Gastroenterol. 2025 Mar 13;8(3):89-96. doi: 10.1093/jcag/gwaf003. eCollection 2025 Jun.

ABSTRACT

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder which can respond to proton-pump inhibitors (PPIs). Genetic variation in the CYP2C19 metabolism gene influences PPI efficacy and adverse effects. Pharmacogenetic testing (PGx) can predict PPI response by analyzing genetic variation, particularly identifying patients categorized as CYP2C19 rapid or ultra-rapid metabolizers who might benefit from PPI dosage increases or changes to pharmacotherapy. Although PGx clinical practice guidelines have been established for PPI use, routine clinical implementation has been slow.

METHODS: We conducted a non-interventional prospective cohort study of patients followed by a paediatric EoE clinic between 2020 and 2023. Eligible patients underwent CYP2C19 PGx testing, with results correlated to PPI use and histological outcomes assessed via endoscopic biopsies.

RESULTS: Sixty-nine patients underwent PGx testing; 20 (29%) and 5 (7%) were determined to be rapid and ultra-rapid metabolizers, respectively. PGx-based management changes were made in 44 (64%) patients. Forty-three (62%) patients completed reassessment endoscopy, of which 21 (49%) demonstrated histological remission; 17 (40%) of these patients achieved remission after PGx-guided drug changes.

CONCLUSIONS: This study demonstrates that PPI non-response in patients with EoE may partly be due to inadequate PPI dosing in those with rapid or ultra-rapid CYP2C19 metabolizer status. Identifying CYP2C19 metabolizer status in pediatric patients with EoE for first-generation PPIs leads to therapeutic management changes and can improve histological remission rates. Clinicians treating EoE patients should consider routine PGx testing in combination with monitoring clinical factors to guide individualized PPI therapy and optimize dosing.

PMID:40567296 | PMC:PMC12188439 | DOI:10.1093/jcag/gwaf003

Int J Mol Sci. 2025 Jun 16;26(12):5746. doi: 10.3390/ijms26125746.

ABSTRACT

The journal corrects the article "Huperzine A Ameliorates Cognitive Deficits in Streptozotocin-Induced Diabetic Rats" [...].

PMID:40565381 | DOI:10.3390/ijms26125746

Int J Mol Sci. 2025 Jun 17;26(12):5817. doi: 10.3390/ijms26125817.

ABSTRACT

Age-related macular degeneration (AMD) is a common cause of blindness worldwide, and it is projected to affect several million individuals by 2040. The human retinal pigment epithelium (hRPE) degenerates in dry AMD, prompting the need to develop stem cell therapies to replace the lost tissue by autologous transplantation and restore the visual function. Nevertheless, the molecular factors behind the hRPE cell fate determination have not been elucidated. Here we identify all molecular determinants of the hRPE cell fate identity by comprehensive and unbiased screening of predicted pioneer factors in the human genome: such TFs mediate coordinated transitions in chromatin accessibility and transcriptional outcome along three major stages of the hRPE genesis. Furthermore, we compile a complete census of all transcription factor-specific binding sites by footprinting analysis of the human epigenome along the RPE developmental trajectory. Gene regulatory networks were found to be involved in cellular responses to glucose and hypoxia, RPE nitrosative stress, type II epithelial-to-mesenchymal transition (EMT), and type III tumorigenic EMT, providing routes for therapeutic intervention on pleiotropic targets dysregulated in AMD, diabetic retinopathy, and cancer progression. Genome editing technologies may leverage this repository to devise functional screenings of regulatory elements and pharmacogenomic therapies in complex diseases, paving the way for strategies in precision medicine.

PMID:40565279 | DOI:10.3390/ijms26125817

Int J Mol Sci. 2025 Jun 9;26(12):5521. doi: 10.3390/ijms26125521.

ABSTRACT

Oleocanthal (OC), a secoiridoid phenolic compound exclusive to extra virgin olive oil (EVOO), has emerged as a promising nutraceutical with multifaceted anti-cancer properties. Despite its well-characterized anti-inflammatory and antioxidant effects, the mechanistic breadth and translational potential of OC in oncology remain underexplored and fragmented across the literature. This comprehensive review synthesizes and critically analyzes recent advances in the molecular, pharmacological, and translational landscape of OC's anti-cancer activities, providing an integrative framework to bridge preclinical evidence with future clinical application. We delineate the pleiotropic mechanisms by which OC modulates cancer hallmarks, including lysosomal membrane permeabilization (LMP)-mediated apoptosis, the inhibition of key oncogenic signaling pathways (c-MET/STAT3, PAR-2/TNF-α, COX-2/mPGES-1), the suppression of epithelial-to-mesenchymal transition (EMT), angiogenesis, and metabolic reprogramming. Furthermore, this review uniquely highlights the emerging role of OC in modulating drug resistance mechanisms by downregulating efflux transporters and sensitizing tumors to chemotherapy, targeted therapies, and immunotherapies. We also examine OC's bidirectional interaction with gut microbiota, underscoring its systemic immunometabolic effects. A major unmet need addressed by this review is the lack of consolidated knowledge regarding OC's pharmacokinetic limitations and drug-drug interaction potential in the context of polypharmacy in oncology. We provide an in-depth analysis of OC's poor bioavailability, extensive first-pass metabolism, and pharmacogenomic interactions, and systematically compile preclinical evidence on advanced delivery platforms-including nanocarriers, microneedle systems, and peptide-drug conjugates-designed to overcome these barriers. By critically evaluating the mechanistic, pharmacological, and translational dimensions of OC, this review advances the field beyond isolated mechanistic studies and offers a strategic blueprint for its integration into precision oncology. It also identifies key research gaps and outlines the future directions necessary to transition OC from a nutraceutical of dietary interest to a viable adjunctive therapeutic agent in cancer treatment.

PMID:40564985 | DOI:10.3390/ijms26125521

Children (Basel). 2025 May 31;12(6):721. doi: 10.3390/children12060721.

ABSTRACT

Background/Objectives: Pharmacogenetic (PGx) testing can predict drug efficacy, toxicity, and risk of adverse drug reactions (ADRs). However, PGx-guided prescribing for pediatric chronic pain is underutilized. Methods: We evaluated the rate of deviance from standard drug dosing regimens in children and adolescents with chronic pain based on PGx testing of drug-metabolizing genes. We also assessed the acceptability and feasibility of PGx testing and implementation of PGx-guided recommendations from patient, caregiver, and prescriber perspectives. Finally, we explored whether PGx results could predict self-reported therapeutic responses and/or ADRs to medications. Results: Forty-eight participants aged 8-17 years with chronic pain provided DNA via buccal swab. Genetic variant data for CYP2D6, CYP2C9, and CYP2C19 metabolism genes and associated metabolizer status were analyzed with respect to clinical PGx guidelines for dosing recommendations of analgesics and psychotropic medications. Participants, their caregivers, and their prescribers also completed quantitative questionnaires evaluating their experience with PGx testing. Twenty-three (50%) participants were predicted to benefit from non-standard dosing for medications with clinical PGx guidelines. Participants expressed satisfaction with the PGx testing process and felt it was safe and worthwhile. Prescribers also reported that PGx results were relevant for medication choices in 42 (91%) participants. Seven (15%) participants had genotyping results which may have predicted their self-reported therapeutic responses and/or ADRs to specific medications. Conclusions: Though further research on pharmacodynamic associations is required to sufficiently address the complexity of interpatient responses to medications for the treatment of pediatric pain and mental health conditions, PGx testing may be used to inform individualized medication choices based on genetic make-up.

PMID:40564679 | DOI:10.3390/children12060721

Bioengineering (Basel). 2025 May 31;12(6):595. doi: 10.3390/bioengineering12060595.

ABSTRACT

Ineffective treatment and side effects are associated with high burdens for the patient and society. We investigated the application of graph representation learning (GRL) for predicting medication usage based on individual genetic data in the United Kingdom Biobank (UKBB). A graph convolutional network (GCN) was used to integrate interconnected biomedical entities in the form of a knowledge graph as part of a machine learning (ML) prediction model. Data from The Pharmacogenomics Knowledgebase (PharmGKB) was used to construct a biomedical knowledge graph. Individual genetic data (n = 485,754) from the UKBB was obtained and preprocessed to match with pharmacogenetic variants in the PharmGKB. Self-reported medication usage labels were obtained from UKBB data field 20003. We hypothesize that pharmacogenetic variants can predict the impact of medications on individuals. We assume that an individual using a medication on a regular basis experiences a net benefit (vs. side-effects) from the medication. ML models were trained to predict medication usage for 264 medications. The GCN model significantly outperformed both a baseline logistic regression model (p-value: 1.53 × 10-9) and a deep neural network model (p-value: 8.68 × 10-8). The GCN model also significantly outperformed a GCN model trained using a random graph (GCN-random) (p-value: 5.44 × 10-9). A consistent trend of medications with higher sample sizes having better performance was observed, and for several medications, a high relative rank of the medication (among multiple medications) was associated with greater than 2-fold higher odds of usage of the medication. In conclusion, a graph-based ML approach could be useful in advancing precision medicine by prioritizing medications that a patient may need based on their genetic data. However, further research is needed to improve the quality and quantity of genetic data and to validate our approach using more reliable medication labels.

PMID:40564412 | DOI:10.3390/bioengineering12060595

Biology (Basel). 2025 Jun 17;14(6):714. doi: 10.3390/biology14060714.

ABSTRACT

Preterm delivery affects approximately 10% of pregnancies worldwide and remains a major clinical challenge due to the lack of reliable early predictive tools. Existing strategies are often invasive, relying on blood or amniotic fluid samples and requiring complex processing. In this study, we describe a novel non-invasive approach based on the multiplex detection of inflammatory cytokines in small urine volumes from pregnant women. To account for clinical and temporal variability, we applied Generalized Additive Models for Location, Scale, and Shape (GAMLSS) to adjust for gestational age at sampling and obstetric factors. Correlation network analyses revealed cytokine interactions that distinguished preterm from term deliveries, with macrophage-derived cytokines-MIP-1α, MIP-1β, IL-15, and IL-22-emerging as central nodes. These findings highlight the involvement of the IL-1 pathway in the pathophysiology of preterm labor. Furthermore, urinary IL-5 and IL-31 levels correlated positively with pregnancy duration, whereas IL-1β and IL-1Ra in urine and TNFα in amniotic fluid showed inverse associations. Altogether, this non-invasive methodology provides insight into immune dynamics during pregnancy and offers a foundation for future studies focused on biomarker discovery and mechanistic understanding of preterm birth.

PMID:40563964 | DOI:10.3390/biology14060714

Hum Genomics. 2025 Jun 25;19(1):71. doi: 10.1186/s40246-025-00780-3.

ABSTRACT

INTRODUCTION: The successful implementation of pharmacogenetics (PGx) in many developed countries has significantly enhanced personalized care and improved both clinical and financial outcomes. This study was designed to evaluate the current knowledge, prevailing attitudes, and perceived ability of pharmacists to actively participate in the integration of PGx into their practice settings.

METHODS: A cross-sectional study was conducted among pharmacists in Yemen using convenience sampling. Data was collected through an online-based questionnaire using the Google Forms platform. Both descriptive and inferential analyses were employed.

RESULTS: With a total of 211 participants involved. Most participants held a bachelor's degree in pharmacy (45%, n = 95). Approximately 70% of respondents reported having between one and five years of experience in pharmacy practice. About three-quarters of pharmacists showed high knowledge score regarding PGx (74.4%; 95% CI: 68.47 - 80.34), with overall pharmacists' knowledge score had a median and IQR of 4( 3-5). The score of knowledge exhibited statistical significance in relation to participants' years of professional experience (p = 0.005). Overall, pharmacists expressed positive attitudes toward PGx. The top two challenges reported for the adoption of PGx in practice were "high cost" and "limited availability of tests". Additionally, about 70% agreed that they lacked knowledge about the specific PGx tests required.

CONCLUSION: Pharmacists exhibit promising attitudes towards PGx. Nevertheless, there is a clear need to reinforce their foundational knowledge and enhance their confidence in the practical application of PGx principles. Effective integration of personalized medicine will necessitate collaborative efforts among key stakeholders, including the Ministry of Health, academic institutions, and professional pharmacy associations.

PMID:40563094 | DOI:10.1186/s40246-025-00780-3

Nat Neurosci. 2025 Jun 25. doi: 10.1038/s41593-025-01998-z. Online ahead of print.

ABSTRACT

Bipolar disorder is a heritable mental illness with complex etiology. While the largest published genome-wide association study identified 64 bipolar disorder risk loci, the causal SNPs and genes within these loci remain unknown. We applied a suite of statistical and functional fine-mapping methods to these loci and prioritized 17 likely causal SNPs for bipolar disorder. We mapped these SNPs to genes and investigated their likely functional consequences by integrating variant annotations, brain cell-type epigenomic annotations, brain quantitative trait loci and results from rare variant exome sequencing in bipolar disorder. Convergent lines of evidence supported the roles of genes involved in neurotransmission and neurodevelopment, including SCN2A, TRANK1, DCLK3, INSYN2B, SYNE1, THSD7A, CACNA1B, TUBBP5, FKBP2, RASGRP1, FURIN, FES, MED24 and THRA among others in bipolar disorder. These represent promising candidates for functional experiments to understand biological mechanisms and therapeutic potential. Additionally, we demonstrated that fine-mapping effect sizes can improve performance of bipolar disorder polygenic risk scores across diverse populations and present a high-throughput fine-mapping pipeline.

PMID:40562893 | DOI:10.1038/s41593-025-01998-z

Biomarkers. 2025 Jun 25:1-17. doi: 10.1080/1354750X.2025.2522892. Online ahead of print.

ABSTRACT

BACKGROUND: Breast cancer (BC) is the most common cancer in women. Taxanes are widely used, but their neurotoxicity affects patients' quality of life. Genetic polymorphisms in CYP450 enzymes influence taxane metabolism, leading to variability in toxicity risk.

METHODS: A literature search was conducted to identify studies on the association between CYP450 polymorphisms and Taxane-Induced Peripheral Neuropathy (TIPN) in BC patients. Odds ratios (OR) and hazard ratios (HR) with 95% confidence intervals (CI) were estimated using a random-effects model in RStudio.

RESULTS: Nine studies with 3034 patients were included. Overall CYP polymorphisms showed a significant association with TIPN (OR: 1.2877, 95% CI: 1.0262-1.6157). CYP1B1 polymorphism had an inconsistent link to TIPN by OR of 1.1524 (95% CI: 0.7441-1.7849). CYP2C8 polymorphism demonstrated the strongest association (OR: 1.5532, 95% CI: 1.2013-2.0082; HR: 1.5236, 95% CI: 1.1317-2.0512). CYP3A4 showed no significant association (OR: 1.0988, 95% CI: 0.5022-2.4404).

CONCLUSIONS: CYP2C8 polymorphisms were significantly linked to TIPN. While CYP1B1 showed inconsistent results, CYP3A4 had no significant association. These findings imply that CYP2C8 genetic variations may affect taxane metabolism and neurotoxicity risk, indicating that pharmacogenomic profiling could help personalize chemotherapy and reduce adverse effects.

PMID:40560854 | DOI:10.1080/1354750X.2025.2522892

Expert Opin Drug Metab Toxicol. 2025 Jun 25. doi: 10.1080/17425255.2025.2525451. Online ahead of print.

ABSTRACT

INTRODUCTION: Rifamycins are a class of antibiotics crucial for the treatment of tuberculosis (TB). Although the development of rifamycin derivatives has revolutionized TB therapy, they are associated with hepatotoxicity, which limits their clinical use.

AREAS COVERED: This review summarizes the development, clinical applications, and hepatotoxicity of rifamycin derivatives. We highlight the mechanisms of rifamycin drug-induced liver injury (DILI) and discuss strategies to improve the safety profiles of rifamycin derivatives. Relevant literature was reviewed by searching PubMed and Scifinder for articles published up to January 2025.

EXPERT OPINION: The hepatotoxicity of rifamycin derivatives remains a challenge in clinical practice. Further research is needed to clarify the detailed mechanisms of rifamycin-induced liver injury. Mechanism-based strategies are also expected to prevent the toxicity of rifamycin derivatives.

PMID:40560789 | DOI:10.1080/17425255.2025.2525451

Naunyn Schmiedebergs Arch Pharmacol. 2025 Jun 25. doi: 10.1007/s00210-025-04334-1. Online ahead of print.

ABSTRACT

Psoriasis is a chronic, immune-mediated inflammatory disorder that significantly impacts patients' quality of life. Oral systemic therapies, including methotrexate, cyclosporine, acitretin, and apremilast, remain integral to psoriasis management, particularly for patients with moderate-to-severe disease who cannot afford biologic therapy. While these treatments are effective, their long-term use is often limited by adverse effects, particularly hepatotoxicity. Methotrexate and acitretin are associated with liver toxicity, requiring regular monitoring, whereas cyclosporine presents a lower but notable risk. Apremilast, a phosphodiesterase 4 inhibitor, offers a safer hepatic profile but has lower efficacy than traditional systemic agents. Emerging therapies, such as TYK2 inhibitors, RORγt inhibitors, and novel PDE4 inhibitors, aim to improve treatment efficacy while minimizing adverse effects. Advances in understanding hepatotoxicity mechanisms have led to identifying predictive biomarkers and hepatoprotective strategies, including antioxidants and non-invasive imaging techniques. Personalized medicine approaches, including pharmacogenomics, are revolutionizing treatment selection by optimizing efficacy while minimizing toxicity risks. This comprehensive review examines oral psoriasis treatments' efficacy and hepatotoxicity profiles, discusses novel therapeutic developments, and explores strategies for mitigating liver-related adverse effects. A balanced approach that integrates clinical monitoring, lifestyle modifications, and emerging precision medicine techniques is essential for optimizing long-term treatment outcomes. Future research should focus on refining predictive models for drug-induced liver injury and developing targeted therapies with improved efficacy and safety profiles.

PMID:40560394 | DOI:10.1007/s00210-025-04334-1

Metabolites. 2025 May 28;15(6):355. doi: 10.3390/metabo15060355.

ABSTRACT

Background/Objectives: Isoniazid (INH) and pyrazinamide (PZA) are first-line drugs used to treat tuberculosis (TB), but their use is generally contraindicated in patients with porphyria, a group of metabolic disorders caused by defects in the heme biosynthetic pathway. To investigate the basis for these contraindications, we compared the effects of INH and PZA on the heme biosynthetic pathway in mouse liver. Method: We investigated the hepatic expression and activity of the key enzymes involved in the heme biosynthetic pathway, including aminolevulinic acid synthase 1 (Alas1) and ferrochelatase (Fech). Additionally, we employed a metabolomic approach to analyze liver and fecal samples from the mice treated with INH or PZA. Result: We found that INH, but not PZA, significantly upregulated the expression and activity of Alas1, the rate-limiting enzyme in heme biosynthesis, while concurrently downregulating Fech, which converts protoporphyrin IX (PPIX) to heme. These changes resulted in the accumulation of the toxic intermediate aminolevulinic acid (ALA) and PPIX in the liver of INH-treated mice. In contrast, PZA had no measurable effect on the expression or function of Alas1 or Fech. Conclusions: These findings provide mechanistic insight into INH-induced porphyria exacerbation and suggest that PZA may not carry the same risk, challenging its current contraindication.

PMID:40559379 | DOI:10.3390/metabo15060355

J Pers Med. 2025 Jun 17;15(6):258. doi: 10.3390/jpm15060258.

ABSTRACT

Background: As more healthcare institutions consider providing preemptive pharmacogenomic (PGx) testing to greater numbers of their patients, it will be important to consider the potential concerns patients may have about the generation of preemptive PGx information. To date, few studies have examined the nature and incidence of patient concerns about preemptive PGx testing. Methods: We conducted a longitudinal survey study of 5000 patients receiving preemptive PGx testing in the Mayo Clinic RIGHT study. We assessed patient concerns regarding issues of data confidentiality, cost implications, comprehension of results, and potential disruption of pre-existing medication regimens. Participants were surveyed before and after they received PGx results from the RIGHT study. Results: We achieved 92.8% and 74.4% response rates on the pre- and post-results surveys, respectively. Participants had low levels of concern about PGx testing overall. However, 25.5% of participants were "quite/extremely concerned" about insurance implications, and 30.1% were "quite/extremely" concerned about increased out-of-pocket costs for prescription medications that might result from PGx testing. These same concerns were significantly reduced on the post-results survey. Patients who initially expressed concerns regarding their ability to understand PGx results were more likely to report having difficulty understanding results on the post-results survey. Conclusions: Our findings suggest that as healthcare institutions look to increase preemptive PGx screening, attention should be given to potential concerns patients may have around such testing. Educational interventions aimed at supporting patient understanding of PGx results and addressing potential concerns will be important elements of a successful PGx program.

PMID:40559120 | DOI:10.3390/jpm15060258

J Pers Med. 2025 Jun 12;15(6):247. doi: 10.3390/jpm15060247.

ABSTRACT

Background: Pharmacogenetics (PGx) is the science of assessing how genetic variation affects drug efficacy, tolerability, and safety. While PGx is an emerging discipline which is becoming standard of care, many providers have misunderstandings about its utility. This is even more of a problem for patients, who may perceive that there is a single drug that is "right" for them. The primary objective of this study was to evaluate consumer comprehension of a newly developed patient-facing PGx report. Methods: In this study, we adapted a commercial pharmacogenetic test (Genomind Professional PGx) into a report intended to be more comprehensible to the consumer. The initial translation of the clinical terminology used in the PGx report, into lay terminology was conducted by PharmDs and PhDs who have collectively provided over 20,000 PGx consults to date. These reports were then evaluated with readability scoring software to ensure each translation's complexity remained ≤8th-grade reading level. A total of 107 participants were recruited to conduct the initial analysis with a goal of achieving a 90% comprehension rate using the Genomind consumer comprehension survey. These participants were also given a modified Minnesota Assessment of Pharmacogenomic Literacy (MAPL™) both before and after the Genomind comprehension survey to assess overall PGx literacy. Results: Ninety-eight (98) out of 107 research participants scored one or zero questions incorrectly, translating to >90% comprehension score on the Genomind consumer comprehension survey. These participants also demonstrated a significant increase in overall pharmacogenetic literacy, as assessed by MAPL after viewing the consumer report and survey. Conclusions: This study found that translating pharmacogenetic test results into lay language may provide individuals with a greater understanding of how their DNA may impact prescribed medications.

PMID:40559109 | DOI:10.3390/jpm15060247

J Pers Med. 2025 Jun 10;15(6):245. doi: 10.3390/jpm15060245.

ABSTRACT

Background/Objectives: The clinical implementation of pharmacogenetics (PGx) remains limited, even for well-established drug-gene interactions. In addition to insufficient infrastructure and PGx education among healthcare professionals, there is currently no consensus regarding which genetic variants should be tested, the most appropriate testing approach (e.g., single-gene vs. multi-gene panels), or how to translate genotypes into actionable therapeutic recommendations. Methods: We describe the implementation of PGx in real daily clinical routine at a single institution to guide other centers. We analyze the drug-gene interactions and genetic variants included in our program based on allelic, genotypic, and phenotypic frequencies, resulting therapeutic recommendations. Linkage disequilibrium and haplotype analyses are also performed. Results and Conclusions: PGx testing was primarily requested by the oncology department. Not all variants included in typical panels had clinical utility in our setting. We do not recommend testing CYP2C19*17 prior to clopidogrel prescription, as it does not translate into a dosing recommendation. TPMT*3B may be considered just to confirm TPMT*3A due to its linkage with TPMT*3C. Similarly, we do not recommend the routine testing of CYP2C9*2 prior to siponimod prescription, as it does not inform therapeutic decisions according to the current drug label.

PMID:40559107 | DOI:10.3390/jpm15060245

J Pers Med. 2025 Jun 3;15(6):232. doi: 10.3390/jpm15060232.

ABSTRACT

Background: Sources and evidence cited to inform payer coverage decisions on pharmacogenomic (PGx) testing in psychiatry are presently underexplored. Methods: We conducted a qualitative and quantitative assessment of publicly available coverage policies from 14 US payers, examining the number and both the type and source of citations across policies and coverage decisions. Payers were classified as for-profit or mutual fund versus non-profit or government, and their coverage decisions were categorized as either coverage (limited or specified) or no coverage. Results: Among 32 unique sources cited, peer-reviewed literature as a single source was most frequently cited across all policies. Of 207 peer-reviewed papers cited across all policies, 40% (n = 83) were psychiatry-specific real-world evidence (RWE) studies. No statistically significant relationships were observed when comparing variance in the number of citations per policy by payer type (p = 0.22) or coverage decision (p = 0.75; unadjusted variance of 61.25 and an adjusted variance of 60.98 for both comparisons). For-profit or mutual fund payers and/or payers providing no coverage cited systematic reviews and non-randomized controlled cohort RWE studies most often. Non-profit or government payers and/or payers providing coverage cited case series or case-control RWE studies most often. Six psychiatry-specific RWE studies and contributions from 13 distinct sources were often cited, regardless of payer type or coverage decision. Conclusions: RWE, among several sources, are cited in many forms and to varying degrees among payers providing coverage decisions for PGx testing in psychiatry, with coverage determinations being largely based on how certain payers interpret evidence on the clinical value of testing.

PMID:40559095 | DOI:10.3390/jpm15060232