Pharmaceuticals (Basel). 2025 May 15;18(5):727. doi: 10.3390/ph18050727.

ABSTRACT

Background/Objectives: Fluoropyrimidines are widely used chemotherapeutic agents in various solid tumors. Germline variants in the DPYD gene, which encodes the enzyme dihydropyrimidine dehydrogenase (DPD), are known to impair drug metabolism and increase the risk of severe toxicity. This umbrella review aims to synthesize the current evidence from systematic reviews on the association between DPYD variants and fluoropyrimidine-induced toxicity. Methods: A comprehensive search was conducted in PubMed, Web of Science, Scopus, and the Cochrane Library from inception to 2023, including gray literature. Systematic reviews assessing fluoropyrimidine toxicity in oncologic patients with DPYD variants were included. Study quality was assessed using the AMSTAR-2 tool. Registration number in PROSPERO: CRD42023401226. Results: Two independent investigators performed the study selection, quality assessment, and data collection. Eight systematic reviews met the inclusion criteria. Methodological confidence was rated as critically low in six, low in one, and medium in another one. The reviews included 125 primary studies, most of them focused on four key DPYD variants (DPYD2*A, DPYD*13, c.2846A>T, and HapB3), all of which showed consistent associations with an increased risk of severe toxicity. Rare variants such as DPYD*4, *5, and *6 were also examined, though evidence remains limited. Pharmacogenetics-guided dosing of fluoropyrimidines significantly reduced toxicity rates in several studies. The integration of DPYD genotyping with phenotyping approaches faces limitations; these tests should complement rather than replace genotyping information. Conclusions: This umbrella review confirms the clinical relevance of DPYD genotyping to predict and mitigate fluoropyrimidine toxicity. Incorporating genotyping into clinical practice, potentially alongside phenotyping and therapeutic drug monitoring, may enhance patient safety and treatment efficacy.

PMID:40430545 | DOI:10.3390/ph18050727

Pharmaceuticals (Basel). 2025 May 2;18(5):677. doi: 10.3390/ph18050677.

ABSTRACT

Background/Objective: Vancomycin, a hydrophilic glycopeptide antibiotic with bactericidal activity against Gram-positive microorganisms, is one of the most commonly used antibiotics un the intensive care unit (ICU). Different efforts have been made to achieve a therapeutically effective plasma concentration of vancomycin by using loading and subsequent maintenance doses on an individual basis, but this remains subject to debate. Our objective was to individualize a dosage regimen in a Chilean ICU to optimize the pharmacological treatment of vancomycin by using a population pharmacokinetic model. Methods: A quantitative descriptive study was carried out in 51 patients at the adult ICU, San Borja Arriarán Clinical Hospital in Santiago, Chile. The dose of vancomycin was calculated by using a population pharmacokinetic software, the Antibiotic Kinetics®, and was subsequently validated with plasma trough levels of the drug through a patient sample. Results: The most commonly prescribed loading dose was 1500 mg and the most commonly used maintenance dose was 1000 mg, three times a day. The measured blood plasma concentrations of each patient (16.98 ± 5.423 μg/mL) were compared with the concentrations calculated through the population pharmacokinetic model (14.33 ± 4.630 μg/mL, p < 0.05). In addition, a correlation was found between the software-calculated trough concentration versus the measured trough concentration for vancomycin, with a positive correlation between both variables established (R2 = 0.65; p < 0.0001). No renal side effects were observed in the treated patient group. Conclusions: In the present study, a vancomycin dosing model for critically ill patients, based on a population pharmacokinetic model, was successfully implemented for routine clinical practice.

PMID:40430496 | DOI:10.3390/ph18050677

Pharmaceuticals (Basel). 2025 Apr 25;18(5):623. doi: 10.3390/ph18050623.

ABSTRACT

Background/Objectives: Methadone maintenance treatment (MMT) is widely used in opioid use disorder (OUD). Its efficacy is influenced by its metabolism, primarily mediated by Cytochrome P450 (CYP450) enzymes in the liver. Genetic polymorphisms in CYP450 genes and other factors, such as age, sex, and concomitant treatments, contribute to interindividual variability in methadone response. This article addresses the relevance of pharmacokinetic biomarkers in methadone metabolism and its impact on treatment outcomes in European populations over the past 25 years. Methods: A systematic review was conducted using four databases (PsycINFO, PubMed, Scopus, and Web of Science) for studies published between 2000 and 2024 following the PRISMA 2020 guidelines (CRD42025641373 in PROSPERO). Two independent reviewers screened and assessed the study quality using NHLBI tools. Discrepancies were solved through consensus. Relevant data including sample size, genetic biomarkers, and key findings were extracted for each study. Data were synthesized and described in detail. Results: Fourteen studies on pharmacogenetic biomarkers influencing methadone metabolism in European populations were analyzed, encompassing a total of 3180 subjects. CYP2B6*6 was identified as a key variant associated with increased (S)-methadone plasma levels, potentially leading to cardiac complications, while the role of other pharmacokinetic genes, including ABCB1 and CYP2D6, was inconclusive. Conclusions: Genetic polymorphisms significantly influence methadone metabolism, with the CYP2B6*6 allele playing a key role in (S)-methadone metabolism and associated with cardiac risks. Pharmacogenetic studies integrating co-mediation-the principal cause of phenoconversion-as a potential variable alongside gender differences and encompassing adequate sample sizes could improve outcomes and establish the basis for personalized medicine of MMT.

PMID:40430443 | DOI:10.3390/ph18050623

J Clin Med. 2025 May 14;14(10):3432. doi: 10.3390/jcm14103432.

ABSTRACT

Porcine peripheral blood mononuclear cells (pPBMCs) are increasingly recognized as a valuable model in biomedical and translational research, particularly in contexts directly related to human health and disease. Their immunological features, such as the presence of CD4+CD8+ double-positive T cells and cytokine expression patterns, exhibit a notable degree of similarity to human immune cells, making them an attractive tool for studying human-relevant immune responses. This review outlines current methodologies for isolating and cryopreserving pPBMCs, with a focus on maintaining high cell viability and functionality. Key technical considerations, including the optimal use of gradient media, appropriate anticoagulants, and standardized freezing/thawing protocols, are discussed in detail. Furthermore, the article highlights the applications of pPBMCs in various research contexts, including vaccine development, inflammation studies, infection models, and xenotransplantation. A comparative perspective is provided to identify similarities and differences between porcine and human PBMCs, supporting the validity of swine as a translational model. Evidence from pPBMC-based studies has shown predictive value for human outcomes, reinforcing their role as a surrogate system for preclinical investigations. Given their anatomical, physiological, and immunogenetic similarities to humans, porcine PBMCs represent a valuable bridge between basic science and clinical application, playing an increasingly important role in translational medicine.

PMID:40429425 | DOI:10.3390/jcm14103432

Genes (Basel). 2025 May 17;16(5):592. doi: 10.3390/genes16050592.

ABSTRACT

BACKGROUND/OBJECTIVES: Pharmacogenomic screening plays a crucial role in optimizing chemotherapy outcomes and minimizing toxicity. Characterizing the baseline distribution of genetic variants in specific populations is essential to inform the prioritization of drug-gene combinations for clinical implementation. The objective of this study was to investigate the distribution of pharmacogenetic variants in 36 genes related to the fluoropyrimidine (FP) pathway among healthy Omani individuals, forming a foundation for future studies in cancer patients receiving FP-based chemotherapy.

METHODS: Ninety-eight healthy Omani participants aged ≥18 years were recruited at the Sultan Qaboos Comprehensive Cancer Care and Research Center. Whole-blood samples were collected, and genomic DNA was extracted. Targeted next-generation sequencing was performed using a custom Ion AmpliSeq panel covering coding exons and splice-site regions of 36 genes involved in FP metabolism and response.

RESULTS: A total of 999 variants were detected across the 36 genes, with 63.3% being heterozygous. The ABCC4 gene had the highest mutation frequency (76 mutations), while DHFR and SMUG1 had the lowest (<10 mutations). In DPYD, four functionally significant variants were found at frequencies ranging from 1 to 8.2% of the population. Missense mutations were also observed in MTHFR and UGT1A1. Three actionable variants in DPYD and MTHFR, associated with 5-fluorouracil and/or capecitabine response, were identified. Additionally, 27 novel single-nucleotide polymorphisms of unknown clinical significance were detected.

CONCLUSIONS: This study reveals key pharmacogenetic variants in the Omani population, underscoring the importance of integrating pharmacogenomic testing into routine care to support safer, more personalized chemotherapy in the region.

PMID:40428413 | DOI:10.3390/genes16050592

Genes (Basel). 2025 Apr 30;16(5):540. doi: 10.3390/genes16050540.

ABSTRACT

A variable number tandem repeat polymorphism has been described in the CYP2C9 promoter (pVNTR) with three types of fragments: short (pVNTR-S), medium (pVNTR-M), and long (pVNTR-L). The pVNTR-S allele appears in strong linkage disequilibrium (LD) with the non-functional CYP2C9*3 allele in populations of European ancestry, but independently of this, it also appears to reduce the level of CYP2C9 expression in human liver by up to 34%.

OBJECTIVES: This study, in a Dominican population with varying amounts of Western European, African, and Native American ancestry, aims primarily to determine the frequency of CYP2C9 pVNTR, and the degree of LD of pVNTR-S with CYP2C9*3. Secondarily, it explores if the frequency of the pVNTR-S allele is over- or under-represented in those with a greater component of African ancestry.

METHODS: A total of 193 healthy volunteers from the Dominican Republic participated in the study. The promoter region of CYP2C9 was amplified and analyzed by capillary electrophoresis. Analyses of CYP2C9 genotypes (*2, *3, *5, *6, and *8) and genetic ancestry, estimated in 176 Dominican individuals by genotyping 90 ancestry informative markers, were previously performed in this population.

RESULTS: The frequencies of CYP2C9 pVNTR-L, M, and S variants are 0.065, 0.896, and 0.039, respectively. LD between pVNTR-S and CYP2C9*3 was found (D' = 0.756, r2 = 0.702) to be weaker than in European populations.

CONCLUSIONS: Populations with a greater African ancestry component appear to present a lower-than-expected frequency of pVNTR-S, as well as a lower tendency for this and CYP2C9*3 alleles to be inherited together, as is common in Europeans. The present exploratory results warrant further research in vivo about the effects of pVNTR-S in predicting CYP2C9 activity. Its inclusion in CYP2C9 testing panels for personalized drug therapy could be relevant in populations such as the Dominican, where the LD between pVNTR-S and CYP2C9*3 is low.

PMID:40428362 | DOI:10.3390/genes16050540

Bioengineering (Basel). 2025 Apr 27;12(5):463. doi: 10.3390/bioengineering12050463.

ABSTRACT

The term "big data analytics (BDA)" defines the computational techniques to study complex datasets that are too large for common data processing software, encompassing techniques such as data mining (DM), machine learning (ML), and predictive analytics (PA) to find patterns, correlations, and insights in massive datasets. Cardiovascular diseases (CVDs) are attributed to a combination of various risk factors, including sedentary lifestyle, obesity, diabetes, dyslipidaemia, and hypertension. We searched PubMed and published research using the Google and Cochrane search engines to evaluate existing models of BDA that have been used for CVD prediction models. We critically analyse the pitfalls and advantages of various BDA models using artificial intelligence (AI), machine learning (ML), and artificial neural networks (ANN). BDA with the integration of wide-ranging data sources, such as genomic, proteomic, and lifestyle data, could help understand the complex biological mechanisms behind CVD, including risk stratification in risk-exposed individuals. Predictive modelling is proposed to help in the development of personalized medicines, particularly in pharmacogenomics; understanding genetic variation might help to guide drug selection and dosing, with the consequent improvement in patient outcomes. To summarize, incorporating BDA into cardiovascular research and treatment represents a paradigm shift in our approach to CVD prevention, diagnosis, and management. By leveraging the power of big data, researchers and clinicians can gain deeper insights into disease mechanisms, improve patient care, and ultimately reduce the burden of cardiovascular disease on individuals and healthcare systems.

PMID:40428082 | DOI:10.3390/bioengineering12050463

Cancers (Basel). 2025 May 20;17(10):1705. doi: 10.3390/cancers17101705.

ABSTRACT

BACKGROUND: Approximately 25.0% of metastatic prostate cancer patients harbour DNA damage repair mutations, including BRCA1 and BRCA2, which are actionable targets for poly(ADP-ribose) polymerase (PARP) inhibitors. Accurate detection of BRCA1/2 mutations is critical for guiding targeted therapies, but crucial pre-analytical factors, such as tissue storage duration and DNA fragmentation, drastically affect the reliability of next-generation sequencing (NGS) using real-world diagnostic specimens.

METHODS: This multicentre study analysed 954 formalin-fixed paraffin-embedded tissue samples from 11 centres, including 559 biopsies and 395 surgical specimens. This study examined the impact of storage duration (<1 year, 1-2 years, and >2 years) and DNA parameters (concentration and fragmentation index) on NGS success rates. Logistic regression and Cox regression analyses were used to assess correlations between these factors and sequencing outcomes.

RESULTS: NGS success rates decreased significantly with longer storage, from 87.8% (<1 year) to 69.1% (>2 years). Samples with higher DNA concentrations and fragmentation indexes had higher success rates (p < 0.001). Surgical specimens had superior success rates (83.3%) compared with biopsies (72.8%) due to better DNA quality. The DNA degradation rate was more pronounced in older samples, underscoring the negative impact of extended storage.

CONCLUSIONS: Timely testing of BRCA1/2 mutations is critical for optimizing the identification of prostate cancer patients eligible for PARP inhibitors. Surgical specimens provide more reliable results than biopsies and minimizing the storage duration significantly enhances testing outcomes. Standardizing pre-analytical and laboratory procedures across centres is essential to ensure personalized treatments and improve patient outcomes.

PMID:40427202 | DOI:10.3390/cancers17101705

Biomedicines. 2025 Apr 28;13(5):1071. doi: 10.3390/biomedicines13051071.

ABSTRACT

Background: The implantation process is complex and involves numerous factors that can affect its success. In artificial reproductive treatments (ARTs), chronic inflammation seems to be associated with implantation failure, largely contributing to reproductive dysfunction. Pentraxin 3 (PTX3) is overexpressed in several pathological conditions by exerting a pivotal role both as a regulator and indicator of inflammatory response. Some literature data have shown that PTX3 could have an impact on follicle growth and development, influencing women's fertility. This study aimed to detect PTX3 in follicular fluids collected during an ART protocol in relation to implantation outcomes. Methods: The PTX3/NF-kB/TLR4 pathway and other cytokines were assessed in the follicular fluid of 169 subjects, under the age of 40 years, undergoing IVF cycles, including females without achieved implantation (n = 98) and those with implantation (n = 71). Furthermore, subgroup analyses were performed to evaluate PTX3 values according to age difference. Results: From our data, PTX3 emerged as a strong predictor, more than TNFα and IL-1β, of implantation failure and related inflammatory follicular state. Overall, the results point to PTX3 as a potential biomarker for ART success, and their testing may be helpful in women whose successful implantation remains unexplained. Conclusions: Therefore, PTX3 could constitute a reliable biomarker and a valuable target to improve ART outcomes.

PMID:40426899 | DOI:10.3390/biomedicines13051071

Brain Sci. 2025 Apr 23;15(5):430. doi: 10.3390/brainsci15050430.

ABSTRACT

BACKGROUND/OBJECTIVES: Precision medicine is not just hype. Instead, it represents a high bar for developing more effective, safer, and better-tolerated therapies in medicine, without exception in psychiatry, including bipolar disorder (BD). A burgeoning body of narrative reviews and perspective papers has already appraised the boundaries of precision medicine in BD.

METHODS: This brief perspective follows a narrative, critical approach focusing explicitly on the antipsychotic management of BD using precision approaches.

RESULTS: While most controversies align with those previously appraised in BD's overall precision medicine approach, specific insights are provided herein.

CONCLUSIONS: Beyond other implications and the strengthened call for valid diagnostic coding systems, the implementation of shared decision-making tools and pharmacogenomics studies focusing on persons with BD are particularly warranted.

PMID:40426603 | DOI:10.3390/brainsci15050430

JAMA Netw Open. 2025 May 1;8(5):e2514278. doi: 10.1001/jamanetworkopen.2025.14278.

ABSTRACT

IMPORTANCE: Available antidepressants provide inadequate therapeutic responses in many patients with major depressive disorder (MDD), highlighting a substantial unmet need.

OBJECTIVE: To evaluate the efficacy and safety of azetukalner, a novel, potent KV7 potassium channel opener, in participants with MDD.

DESIGN, SETTING, AND PARTICIPANTS: X-NOVA was a multicenter, proof-of-concept, phase 2, randomized, double-blind, parallel-group, placebo-controlled clinical trial that evaluated azetukalner in participants (adults aged ≥18 to ≤65 years) with moderate to severe MDD in a current depressive episode. Participants were enrolled between April 2022 and October 2023, and data analysis occurred from January 2023 to January 2024.

INTERVENTION: Participants were randomized (1:1:1) to 10 mg of azetukalner, 20 mg of azetukalner, or placebo orally once daily with food for 6 weeks, with a 4-week follow-up. Concomitant antidepressant medications were not permitted.

MAIN OUTCOMES AND MEASURES: The primary efficacy end point was change in Montgomery-Åsberg Depression Rating Scale (MADRS) score at week 6. Secondary end points included change from baseline at week 6 in the Snaith-Hamilton Pleasure Scale (SHAPS) and Beck Anxiety Inventory. Exploratory end points included change in the Hamilton Depression Rating Scale, 17-Item (HAM-D17) score and change in MADRS at week 1. Frequency and severity of treatment-emergent adverse events (TEAEs) were recorded.

RESULTS: Altogether, 168 participants were randomized (56 to placebo, 56 to 10 mg of azetukalner, and 56 to 20 mg of azetukalner); mean (SD) age was 47.2 (13.6) years, and 111 participants (66.5%) were female. The modified intent-to-treat and safety populations consisted of 164 and 167 participants, respectively. The mean (SE) reduction in MADRS scores from baseline to week 6 was -13.90 (1.41) points with placebo, -15.61 (1.34) points with 10 mg of azetukalner, and -16.94 (1.45) points with 20 mg of azetukalner; the mean (SE) reduction with 20 mg of azetukalner vs placebo was clinically meaningful but not statistically significant (-3.04 points; 95% CI, -7.04 to 0.96 points; P = .14) at week 6, while significant at week 1 (-2.66 points; 95% CI, -5.30 to -0.03 points; P = .047). The mean (SE) reduction in HAM-D17 from baseline to week 6 was significantly greater with 20 mg of azetukalner vs placebo (-13.3 [1.1] vs -10.2 [1.0] points; P = .04). The mean (SE) reduction in SHAPS scores from baseline to week 6 was significantly greater with 20 mg of azetukalner vs placebo (-7.77 [0.87] vs -5.30 [0.85] points; P = .046). Similar rates of discontinuation due to TEAEs were reported across groups.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of azetukalner, preliminary findings supported its further clinical development for the treatment of MDD and anhedonia.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05376150.

PMID:40423966 | PMC:PMC12117446 | DOI:10.1001/jamanetworkopen.2025.14278

J Neurol. 2025 May 27;272(6):423. doi: 10.1007/s00415-025-13108-x.

NO ABSTRACT

PMID:40423827 | DOI:10.1007/s00415-025-13108-x

Neurol Int. 2025 Apr 24;17(5):65. doi: 10.3390/neurolint17050065.

ABSTRACT

Background/Objectives: Several genetic factors are related to the risk of Alzheimer's disease (AD) and the response to cholinesterase inhibitors (ChEIs) (donepezil, galantamine, and rivastigmine) or memantine. However, findings have been controversial, and, to the best of our knowledge, admixed populations have not been previously evaluated. We aimed to determine the impact of genetic and non-genetic factors on the risk of AD and the short-term response to ChEIs and memantine in patients with AD from Mexico. Methods: This study included 117 patients from two specialty hospitals in Mexico City, Mexico. We evaluated cognitive performance via clinical evaluations and neuropsychological tests. Nineteen variants in ABCB1, ACHE, APOE, BCHE, CHAT, CYP2D6, CYP3A5, CHRNA7, NR1I2, and POR were assessed through TaqMan assays or PCR. Results: Minor alleles of the ABCB1 rs1045642, ACHE rs17884589, and CHAT rs2177370 and rs3793790 variants were associated with the risk of AD; meanwhile, CHRNA7 rs6494223 and CYP3A5 rs776746 were identified as low-risk variants in AD. BCHE rs1803274 was associated with worse cognitive functioning. None of the genetic and non-genetic factors studied were associated with the response to pharmacological treatment. Conclusions: We identified potential genetic variants related to the risk of AD; meanwhile, no factor was observed to impact the response to pharmacological therapy in patients with AD from Mexico.

PMID:40423221 | DOI:10.3390/neurolint17050065

J Pers Med. 2025 May 2;15(5):185. doi: 10.3390/jpm15050185.

ABSTRACT

Background/Objectives: Solid organ transplant (SOT) recipients are exposed to multiple medications, many of which have pharmacogenetic (PGx) prescribing recommendations. This study leveraged data from a population-scale biobank and an enterprise data warehouse to determine the prevalence of actionable exposures to PGx medications among kidney, heart, and lung transplant recipients during the first six months post-transplant. Methods: We conducted a retrospective analysis of adult SOT patients with genetic data available from the Colorado Center for Personalized Medicine (CCPM) biobank and clinical data from Health Data Compass (HDC). We evaluated 29 variants in 13 pharmacogenes and 42 Clinical Pharmacogenetics Implementation Consortium (CPIC) level A or B medications (i.e., sufficient evidence to recommend at least one prescribing action based on genetics). The primary outcome was actionable exposure to a PGx medication (i.e., actionable phenotype and a prescription for an affected PGx medication). Results: The study included 358 patients. All patients were prescribed at least one PGx medication, and 49.4% had at least one actionable exposure to a PGx medication during the first six months post-transplant. The frequency of actionable exposure was highest for tacrolimus (15.4%), followed by proton pump inhibitors (PPIs) (15.1%) and statins (12.8%). Statin actionable exposures significantly differed by transplant type, likely due to variations in prescribing patterns and actionable phenotypes for individual statins. Conclusions: Our findings highlight the potential clinical utility of PGx testing among SOT patients. Further studies are needed to address the impact on clinical outcomes and the optimal timing of PGx testing in the SOT population.

PMID:40423057 | DOI:10.3390/jpm15050185

Metabolites. 2025 May 13;15(5):323. doi: 10.3390/metabo15050323.

ABSTRACT

Background/Objectives: Metabolomics, in combination with genetic data, is a powerful approach to study the biochemical consequences of genetic variation. We assessed the impact of human gene knockouts (KOs) on the metabolite levels of Estonia Biobank (EstBB) participants and integrated the results with electronic health record data. Methods: In 150,000 EstBB genotyped participants, we identified 723 KOs with 152 different predicted loss of function (pLoF) variants in 115 genes. For those KOs and 258 controls, 1387 metabolites were profiled using ultra-high-performance liquid chromatography-tandem mass spectrometry. Results: We identified 48 associations linking rare pLoF variants in 22 genes to 43 metabolites. Out of 48 associations, 27 (56%) were found in genes that cause inborn errors of metabolism. The top associations identified in our analysis included genes and metabolites involved in the degradation pathway of the pyrimidine bases uracil and thymine (DPYD and UPB1). We found DPYD gene KOs to be associated with elevated levels of Uracil, confirming that DPD-deficiency is a leading cause of severe 5-Fluorouracil toxicity. Overall, 54% of reported associations are gene targets of approved drugs or bioactive drug-like compounds. Conclusions: Our findings contribute to assessing the impact of human KOs on metabolite levels and offer insights into gene functions, disease mechanism, and drug target validation.

PMID:40422899 | DOI:10.3390/metabo15050323

Pharmacogenomics. 2025 May 27:1-24. doi: 10.1080/14622416.2025.2504865. Online ahead of print.

ABSTRACT

Pharmacogenomics (PGx) has the potential to revolutionize hypertension management by tailoring antihypertensive therapy based on genetic profiles. Despite significant advances in genomic research, the clinical translation of PGx in hypertension remains challenging due to genetic complexity, variability in drug response, and implementation barriers. This review explores the genetic basis of hypertension, highlighting key pharmacogenomic markers that influence antihypertensive metabolism and efficacy, including CYP2D6, CYP3A4, UMOD, and ACE polymorphisms. We also examine the role of Mendelian randomization, polygenic risk scores in drug development and stratifying hypertension treatment response. While PGx offers opportunities for personalized medicine - such as reducing trial-and-error prescribing and improving adherence - several obstacles hinder its widespread adoption. These include limited clinical actionability, lack of large-scale randomized controlled trials, cost constraints, and concerns about equity and accessibility. Furthermore, drug-gene interactions and phenoconversion add complexity to implementation. Emerging technologies, including artificial intelligence-driven prescribing, microbiome integration, and pharmacoepigenomics, may enhance PGx precision in hypertension management. However, further research, clinical validation, and policy frameworks are necessary before PGx can be routinely incorporated into hypertension care. This review critically evaluates both the promise and limitations of PGx in hypertension, offering insights into the future of precision medicine in cardiovascular health.

PMID:40421951 | DOI:10.1080/14622416.2025.2504865

Pharmacogenet Genomics. 2025 Jul 1;35(5):170-171. doi: 10.1097/FPC.0000000000000565. Epub 2025 May 27.

NO ABSTRACT

PMID:40421730 | DOI:10.1097/FPC.0000000000000565

Drug Metab Pers Ther. 2025 May 23. doi: 10.1515/dmpt-2025-0008. Online ahead of print.

ABSTRACT

OBJECTIVES: Macrophages play a major role in the inflammation. Recently, the expression of some cytochrome P450 (CYP450) 4 family enzymes was identified in the macrophages including CYP4V2, which metabolizes saturated fatty acids. Lauric acid is unsaturated fatty acid, which can induce inflammation. Its effect on the expression of CYP4V2 and the inflammatory mediators in macrophages is still unknown. This study aims to investigate the effect of lauric acid on the expression of CYP4V2 and cyclo-oxygenase 2 (COX2) in the human monocytes and macrophage THP1 cell line.

METHODS: The THP1 monocyte cell line was differentiated into macrophages using 100 ng/mL PMA. Then, the cells were treated with 10 µM lauric acid for 72 h. The mRNA and protein expression of human CYP4V2 and COX2 were analyzed using real-time and western blot techniques, respectively.

RESULTS: It was found that the mRNA and protein expression of CYP4V2 was upregulated after treatment of the macrophages with lauric acid in a dose-dependent manner. This upregulation was correlated with the expression of COX2.

CONCLUSIONS: It can be concluded from the results of this study that mRNA and protein expression of CYP4V2 are upregulated by lauric acid in correlation with the induction of inflammation. CYP4V2 can play a role in the inflammation process managed by macrophages.

PMID:40421601 | DOI:10.1515/dmpt-2025-0008

Pharmacogenet Genomics. 2025 May 27. doi: 10.1097/FPC.0000000000000570. Online ahead of print.

ABSTRACT

Propofol is commonly used to sedate patients, but variations in how individuals metabolize the drug may affect dosing requirements. The objective of this study was to explore how genetic variations in CYP450 enzymes, particularly CYP2B6, influence propofol metabolism in ICU patients receiving mechanical ventilation. Genetic variants of CYP2B6, CYP2C9, CYP2C19, and CYP3A5 were collected from an institutional genetic data repository. Patients were dichotomized into low and high metabolic activity for each enzyme, and the mean weight- and time-normalized propofol dose administered was compared between groups via t test. There was no significant difference in average daily propofol dose between patients with low and high CYP2B6 activity (11 vs. 11 mg/kg/h, P = 0.78), or any of the other CYP enzymes analyzed (all P > 0.05). This study could not replicate previous studies indicating that patients carrying genetic variants with diminished CYP2B6 activity required lower propofol doses. Future studies with prospectively collected dosing and outcomes data, and measurement of plasma drug concentrations, may provide insights into personalized propofol dosing strategies.

PMID:40421567 | DOI:10.1097/FPC.0000000000000570

Front Cardiovasc Med. 2025 May 12;12:1572389. doi: 10.3389/fcvm.2025.1572389. eCollection 2025.

ABSTRACT

BACKGROUND: Variability in responses to clopidogrel and aspirin therapy for coronary artery disease has driven interest in pharmacogenomics. This study investigates the role of genetic variants in CYP2C19, ABCB1, and PON1 in predicting adverse cardiovascular events and guiding personalised antiplatelet therapy.

METHODS: A retrospective cohort study designed to compare the effectiveness and safety of the risk levels from CYP2C19 (*2, *3, *17), ABCB1 C3435T, and PON1 Q192R polymorphisms. The primary outcome was the incidence of haemorrhage and major adverse cardiovascular events (MACE). Kaplan Merir curves and Cox regression with IPTW adjustments were used for analysis.

RESULTS: The results of this study indicate that patients in Group A, who received treatment consistent with multigene testing (CYP2C19, ABCB1, and PON1), experienced significantly lower major adverse cardiovascular events (MACE) compared to Group B. Multigene testing proved to be more accurate in predicting clopidogrel effectiveness and reducing adverse events without an increased risk of haemorrhage (HR 0.671, 95% CI: 0.526-0.855, P = 0.001). Patients in Group A showed no significant difference in haemorrhage risk compared to Group B, with an HR of 0.831 (95% CI: 0.598-1.155, P = 0.271) after adjustment.

CONCLUSION: Multigene-guided antiplatelet therapy is more effective in reducing adverse cardiovascular events. Further prospective studies are needed to validate these findings, incorporating genetic, environmental, and lifestyle factors for a comprehensive personalised medicine approach.

PMID:40421189 | PMC:PMC12104257 | DOI:10.3389/fcvm.2025.1572389