Methods Protoc. 2025 Mar 4;8(2):27. doi: 10.3390/mps8020027.

ABSTRACT

Genetic profiling and molecular biology methods have made it possible to study the etiology of the end-stage organ disease that led to transplantation, the genetic factors of compatibility and tolerance of the transplant, and the pharmacogenetics of immunosuppressive drugs and allowed for the development of monitoring methods for the early assessment of allograft rejection. This study aims to report the design and baseline characteristics of an integrated personalized genetic approach in solid organ transplantation, including whole-exome sequencing (WES) and the monitoring of dd-cfDNA by dPCR. Preliminary results reported female recipients with male donors undergoing two pediatric and five adult kidney and three heart transplantations. WES revealed a pathogenic mutation in RBM20 and VUS in TTN and PKP2 in heart recipients, while kidney donors presented mutations in UMOD and APOL1 associated with autosomal-dominant kidney diseases, highlighting the risks requiring the long-term monitoring of recipients, donors, and their family members. %dd-cfDNA levels were generally stable but elevated in cadaveric kidney recipient and one pediatric patient with infectious complications and genetic variants in the ABCB1 and ABCC2 genes. These findings highlight the potential of combining genetic and molecular biomarker-based approaches to improve donor-recipient matching, predict complications, and personalize post-transplant care, paving the way for precision medicine in transplantation.

PMID:40126245 | DOI:10.3390/mps8020027

J Allergy Clin Immunol Glob. 2025 Feb 12;4(2):100439. doi: 10.1016/j.jacig.2025.100439. eCollection 2025 May.

ABSTRACT

BACKGROUND: Patients with severe asthma may demonstrate reduced sensitivity to steroid treatment. However, the implications of this reduced responsiveness for clinical outcomes and the underlying mechanisms remain unclear.

OBJECTIVE: The aim of this study was to investigate whether steroid sensitivity in patients with asthma is related to severity and clinical outcomes and to elucidate the role of inflammatory pathways in reducing steroid sensitivity.

METHODS: This observational study of 169 asthma patients, with 161 followed for 1 year, involved isolation of peripheral blood mononuclear cells. These cells were treated with dexamethasone, and the mRNA expression of FKBP5, which is a marker of steroid sensitivity, was measured. To explore the mechanism underlying the reduced steroid sensitivity, cells were exposed to PI3K and MAPK inhibitors in combination with dexamethasone.

RESULTS: A total of 53 patients diagnosed with severe asthma exhibited markedly diminished sensitivity to steroids compared with those with nonsevere asthma. Reduced steroid sensitivity has emerged as a critical risk factor for failure to experience clinical remission and exacerbation. This relationship between reduced steroid sensitivity and disease severity and adverse outcomes was confirmed at the 1-year follow-up. Mechanistic investigations revealed that the degree of recovery from steroid sensitivity after PI3Kδ/γ inhibitor treatment was significantly greater in patients with severe asthma than in those with nonsevere asthma, a finding confirmed at the 1-year follow-up.

CONCLUSIONS: Patients with severe asthma demonstrate reduced steroid sensitivity, which results in unfavorable clinical outcomes. Conversely, inhibition of the PI3K pathway significantly improves steroid sensitivity.

PMID:40125453 | PMC:PMC11928809 | DOI:10.1016/j.jacig.2025.100439

iScience. 2025 Feb 22;28(3):112076. doi: 10.1016/j.isci.2025.112076. eCollection 2025 Mar 21.

ABSTRACT

Antibiotic activity against intracellular pathogens is commonly evaluated in static models that do not reproduce plasma concentration fluctuations. However, efficacy is influenced by exposure conditions, related to drug pharmacokinetic profile. This study developed and validated an intracellular pharmacodynamic model using the hollow fiber system, the gold standard for evaluating extracellular antibiotic activity. The activity of fluoroquinolones, i.e., bactericidal antibiotics with intracellular tropism, was studied against intracellular Staphylococcus aureus, involved in persistence/recurrence of infections. In this model, moxifloxacin was more effective than in static conditions (0.87 log10 killing gain), while ciprofloxacin kill rate was slower (18 vs. 12 h to achieve 1 log10 killing). These differences were linked to the Cmax/MIC ratio, which was 2.5-fold higher for moxifloxacin but 3.4-fold lower for ciprofloxacin in dynamic vs. static conditions. This model could be applied to other drugs, cell types, or pathogens, offering a tool for optimizing dosing schemes and considering intracellular reservoirs.

PMID:40124509 | PMC:PMC11930174 | DOI:10.1016/j.isci.2025.112076

Chin J Nat Med. 2025 Mar;23(3):368-376. doi: 10.1016/S1875-5364(25)60837-5.

ABSTRACT

In this study, we employed a combination of genome mining and heteronuclear single quantum coherence (HSQC)-based small molecule accurate recognition technology (SMART) technology to search for fernane-type triterpenoids. Initially, potential endophytic fungi were identified through genome mining. Subsequently, fine fractions containing various fernane-type triterpenoids were selected using HSQC data collection and SMART prediction. These triterpenoids were then obtained through targeted isolation and identification. Finally, their antifungal activity was evaluated. As a result, three fernane-type triterpenoids, including two novel compounds, along with two new sesquiterpenes and four known compounds were isolated from one potential strain, Diaporthe discoidispora. Their structures were elucidated through analysis of high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and nuclear magnetic resonance (NMR) spectroscopic data. The absolute configurations were determined using single-crystal X-ray diffraction analysis and electron capture detector (ECD) analysis. Compound 3 exhibited moderate antifungal activity against Candida albicans CMCC 98001 and Aspergillus niger.

PMID:40122666 | DOI:10.1016/S1875-5364(25)60837-5

Eur J Pharmacol. 2025 Mar 20:177533. doi: 10.1016/j.ejphar.2025.177533. Online ahead of print.

ABSTRACT

BACKGROUND: The antibiotic salinomycin, a well-known cancer stem cell inhibitor, may impact the diversity of the intestinal microbiota in colorectal cancer (CRC) mice, which plays a pivotal role in shaping the immune system. This study explores the anti-cancer effects and mechanisms of combining salinomycin and fecal microbiota transplantation (FMT) in treating CRC.

METHODS: FMT was given via enema, while salinomycin was injected intraperitoneally into the CRC mouse model induced by azoxymethane/dextran sodium sulfate.

RESULTS: In CRC mice, a large number of LGR5-labeled cancer stem cells and severe disturbances in the intestinal microbiota were observed. Interestingly, salinomycin inhibited the proliferation of cancer stem cells without exacerbating the microbial disorder as expected. In comparison to salinomycin treatment, the combination of salinomycin and FMT significantly improved pathological damage and restored intestinal microbial diversity, which is responsible for shaping the anti-cancer immune microenvironment. The supplementation of FMT significantly increased the levels of propionic acid and butyric acid while also promoting the infiltration of CD8+ T cells and Ly6G+ neutrophils, as well as reducing F4/80+ macrophage recruitment. Notably, cytokines that were not impacted by salinomycin exhibited robust reactions to alterations in the gut microbiota. These included pro-inflammatory factors (IL6, IL12b, IL17, and IL22), chemokine-like protein OPN, and immunosuppressive factor PD-L1.

CONCLUSIONS: Salinomycin plays the role of "eliminating pathogenic qi," targeting cancer stem cells; FMT plays the role of "strengthening vital qi," reversing the intestinal microbiota disorder and enhancing anti-cancer immunity. They have a synergistic effect on the development of CRC.

PMID:40120791 | DOI:10.1016/j.ejphar.2025.177533

Pediatr Blood Cancer. 2025 Mar 22:e31668. doi: 10.1002/pbc.31668. Online ahead of print.

ABSTRACT

BACKGROUND: L-asparaginase is essential in treating pediatric acute lymphoblastic leukemia (ALL) but is limited by hypersensitivity reactions in up to 70% of patients, leading to severe, dose-limiting complications and compromised event-free survival.

PROCEDURE: This study conducted a genome-wide association study (GWAS) in a discovery cohort of 221 pediatric cancer patients who experienced l-asparaginase-induced hypersensitivity reactions (≥CTCAE grade 2) and 705 controls without hypersensitivity despite equivalent exposure. Results were replicated in an independent cohort of 41 cases and 139 controls.

RESULTS: Significant associations were identified between hypersensitivity and four genes crucial for amino acid stress response: CYP1B1 (rs59569490; odds ratio [OR] = 8.5; 95% confidence interval [CI], 3.9-18.5; p = 1.5 × 10-10), SEC16B (rs115461320; OR = 4.2; 95% CI, 2.5-7.9; p = 1.2 × 10-6), OPLAH (rs11993268; OR = 4.8; 95% CI, 2.4-9.9; p = 2.0 × 10-6), and SORCS2 (rs11940340; OR = 6.7; 95% CI, 2.8-15.7; p = 5.7 × 10-7). Variants in SEC16B, OPLAH, and SORCS2 remained significant in the analysis of the replication cohort (p < 0.05). Patients who carried risk alleles in two or more of these genes experienced an 86.4% increased incidence of hypersensitivity reactions in the discovery cohort (OR = 25.2; 95% CI, 7.4-86.2; p = 1.0 × 10-10), which was replicated in the independent cohort with a 100% incidence in carriers (p = 0.04).

CONCLUSIONS: The cumulative incidence of these large effect variants highlights their significance for the identification of patients at high risk of l-asparaginase-induced hypersensitivity. Successfully identifying patients at increased risk of hypersensitivity reactions can inform personalized treatment strategies and limit these harmful dose-limiting reactions in pediatric ALL.

PMID:40119746 | DOI:10.1002/pbc.31668

Bioanalysis. 2025 Mar 21:1-13. doi: 10.1080/17576180.2025.2481019. Online ahead of print.

ABSTRACT

Pharmacogenomics (PGx) is transforming therapeutic development by providing insights into how genetic variations influence drug response, safety, and efficacy. This review provides a structured analysis of PGx in clinical research, beginning with an overview of key genes involved in drug metabolism, transport, and targets. Following this, it examines strategies for identifying PGx-relevant genes, including phenotype-driven, hypothesis-driven, population-focused, and clinical-driven approaches. Technical platforms such as PCR, MassARRAY, and next-generation sequencing are analyzed for their suitability in PGx studies. The discussion then shifts to assay validation processes, covering both analytical and clinical validation, to ensure data reliability in clinical trials. Finally, regulatory expectations for PGx in clinical trials are discussed, focusing on key requirements across all phases of drug development. This review aims to provide a clear and practical framework for integrating PGx into clinical research to enhance drug safety, efficacy, and personalized medicine.

PMID:40118816 | DOI:10.1080/17576180.2025.2481019

Parkinsonism Relat Disord. 2025 Mar 14:107774. doi: 10.1016/j.parkreldis.2025.107774. Online ahead of print.

NO ABSTRACT

PMID:40118710 | DOI:10.1016/j.parkreldis.2025.107774

Am J Vet Res. 2025 Mar 21:1-9. doi: 10.2460/ajvr.24.12.0377. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine the population variability in dextromethorphan metabolism by cytochrome (CY) P450 2D15 (CYP2D15) in dogs.

METHODS: Healthy pet dogs were recruited from 2018 through 2024 from the Inland Pacific Northwest and phenotyped by orally administering the Program in Individualized Medicine cocktail, which contains dextromethorphan, a CYP2D15-specific probe drug. Glucuronidase-treated urine samples collected 6 hours after dosing were assayed for dextromethorphan and dextrorphan concentrations. Log-transformed metabolic ratios of dextrorphan divided by dextromethorphan (DOR/DXM Log MRs) were calculated. Dogs were genotyped for 5 missense CYP2D15 variants. Univariate and multivariate statistical approaches were used to evaluate associations between DOR/DXM Log MRs and demographic variables.

RESULTS: 105 dogs, including 34 mixed breeds and 71 dogs from 20 different owner-designated breeds, were enrolled and completed the study. There was a wide distribution of DOR/DXM Log MRs, from 0.97 to 2.76, representing a log unit range of 1.8 (63-fold variation DOR/DXM Log MRs). Log-transformed metabolic ratios of dextrorphan divided by dextromethorphan were normally distributed and unimodal. The mean (± SD) DOR/DXM Log MR was 2.04 ± 0.37. Multiple linear regression analysis showed significant association (R2 = 0.16) between DOR/DXM Log MRs and dog breed for Golden Retrievers (2.26 ± 0.29; N = 23) and Pugs (1.47 ± 0.29; N = 3). Log-transformed metabolic ratios of dextrorphan divided by dextromethorphan were not associated with dog sex, age, weight, or genotype.

CONCLUSIONS: There is substantial variability in DOR/DXM Log MR values among individuals, which can be partially attributed to differences between breeds.

CLINICAL RELEVANCE: These findings predict high variability in the metabolism of drugs by CYP2D15 associated with differences between dog breeds.

PMID:40118021 | DOI:10.2460/ajvr.24.12.0377

Mol Divers. 2025 Mar 21. doi: 10.1007/s11030-025-11168-9. Online ahead of print.

ABSTRACT

Vitamin D receptor (VDR) agonists play a pivotal role in modulating immune responses and promoting melanocyte survival, making them potential candidates for vitiligo treatment. The VDR gene is integral to mediating the effects of vitamin D in the immune system, and disruptions in its structure due to missense mutations may significantly contribute to the pathogenesis of vitiligo. Missense single-nucleotide polymorphisms (SNPs) can alter the amino acid sequence of the VDR protein, potentially affecting its ligand-binding affinity and downstream signaling. Investigating these missense SNPs provides critical insights into the genetic underpinnings of vitiligo and may help identify biomarkers for early detection and precision-targeted therapies. This study explored the therapeutic potential of vitamin D analogs in vitiligo management, with a particular focus on their binding interactions and molecular efficacy. Using molecular docking and virtual screening, 24 vitamin D analogs were evaluated. Calcipotriol exhibited the highest binding affinity (-11.4 kcal/mol) and unique interactions with key residues in the VDR ligand-binding domain. Additionally, an analysis of structural variations stemming from missense mutations in the VDR gene highlighted potential impacts on receptor-ligand interactions, further emphasizing the importance of genetic factors in treatment response. These findings underscore the potential of calcipotriol to promote melanogenesis and modulate pigmentation in vitiligo. A comparative analysis identified structural variations influencing the efficacy of other analogs, such as calcitriol and tacalcitol. Although the in silico methods provided valuable insights, the study acknowledges the limitations of excluding dynamic cellular environments and emphasizes the need for experimental validation. Overall, this study enhances our understanding of VDR-targeted therapies, and calcipotriol is a promising candidate for further development in the management of vitiligo.

PMID:40117094 | DOI:10.1007/s11030-025-11168-9

Int J Clin Pharm. 2025 Mar 21. doi: 10.1007/s11096-025-01899-y. Online ahead of print.

ABSTRACT

BACKGROUND: Achieving optimal tacrolimus dosing is vital for effectively balancing therapeutic efficacy and safety, as CYP3A5 genetic variants and inter-patient variability emphasize the need for precision strategies.

AIM: This study aimed to optimize tacrolimus dosage prediction for renal transplant recipients by incorporating genetic polymorphisms, specifically profiling CYP3A5 genetic variants, within the DoseOptimal framework to enhance interpretability and accuracy of dosing decisions.

METHOD: The dataset comprised clinical, demographic, and CYP3A5 genetic variants information from 1045 stable tacrolimus-treated patients. The DoseOptimal framework was developed by integrating the strengths of the most effective algorithms from fifteen machine learning models. SHapley Additive exPlanations (SHAP) and decision tree insights were incorporated to enhance the framework's interpretability. The framework's performance was assessed using mean absolute error (MAE) and the coefficient of determination (R2 score). The F-statistic and p value were calculated to validate the framework's statistical significance.

RESULTS: The DoseOptimal framework demonstrated robust performance with an R2 score of 0.884 in the training set and 0.830 in the testing set. The MAE was 0.40 mg/day (95% CI 0.38-0.43) in the training set and 0.41 mg/day (95% CI 0.38-0.45) in the testing set. The framework predicted the ideal tacrolimus dosage in 87.6% (n = 275) of the test cohort, with 3.2% (n = 10) underestimation and 9.2% (n = 29) overestimation. The framework's statistical significance was confirmed with an F-statistic of 266.095 and a p value < 0.001.

CONCLUSION: The framework provides precision medicine-based dosing solutions tailored to individual genetic profiles, minimizing dosing errors and enhancing patient outcomes.

PMID:40117041 | DOI:10.1007/s11096-025-01899-y

Eur J Clin Pharmacol. 2025 Mar 21. doi: 10.1007/s00228-025-03821-x. Online ahead of print.

ABSTRACT

PURPOSE: Direct oral anticoagulants (DOACs) are used to prevent and treat thromboembolic events in adults. We aimed to investigate whether pharmacogenomic variation contributes to the risk of bleeding during DOAC treatment.

METHODS: Cases were recruited from reports of bleeding sent to the Swedish Medical Products Agency (n = 129, 60% men, 93% Swedish, 89% on factor Xa inhibitors) and compared with population controls (n = 4891) and a subset matched for exposure to DOACs (n = 353). We performed a genome-wide association study, with analyses of candidate single nucleotide polymorphisms (SNPs) and candidate gene set analyses.

RESULTS: Forty-four cases had major, 37 minor, and 48 clinically relevant non-major (CRNM) bleeding. When cases were compared with matched controls, BAIAP2L2 rs142001534 was significantly associated with any bleeding and major/CRNM bleeding (P = 4.66 × 10-8 and P = 3.28 × 10-8, respectively). The candidate SNP CYP3A5 rs776746 was significantly associated with major and major/CRNM bleeding (P = 0.00020 and P = 0.00025, respectively), and ABCG2 rs2231142 was nominally associated with any bleeding (P = 0.01499). Rare coding variants in the candidate gene VWF were significantly associated with any bleeding (P = 0.00296).

CONCLUSION: BAIAP2L2, CYP3A5, ABCG2, and VWF may be associated with bleeding in DOAC-treated patients. The risk estimates of the candidate variants in CYP3A5 and ABCG2 were in the same direction as in previous studies. The Von Willebrand Factor gene (VWF) is linked to hereditary bleeding disorders, while there is no previous evidence of bleeding associated with BAIAP2L2.

PMID:40116934 | DOI:10.1007/s00228-025-03821-x

Pharmacogenomics. 2025 Mar 21:1-20. doi: 10.1080/14622416.2025.2481025. Online ahead of print.

ABSTRACT

AIM: To systematically assess clinical studies involving patients undergoing drug therapy, comparing different genotypes to assess the relationship with changes in QT intervals, with no limitations on study design, setting, population, dosing regimens, or duration.

METHODS: This systematic review followed PRISMA guidelines and a pre-registered protocol. Clinical human studies on PGx markers of diQTP were identified, assessed using standardized tools, and categorized by design. Gene associations were classified as pharmacokinetic or pharmacodynamic. Identified genes underwent pathway enrichment analyses. Drugs were classified by third-level Anatomical Therapeutic Chemical (ATC) codes. Descriptive statistics were computed by study category and drug classes.

RESULTS: Of 4,493 reports, 84 studies were included, identifying 213 unique variants across 42 drug classes, of which 10% were replicated. KCNE1-Asp85Asn was the most consistent variant. Most findings (82%) were derived from candidate gene studies, suggesting bias toward known markers. The diQTP-associated genes were mainly linked to "cardiac conduction" and "muscle contraction" pathways (false discovery rate = 4.71 × 10-14). We also found an overlap between diQTP-associated genes and congenital long QT syndrome genes.

CONCLUSION: Key genes, drugs, and pathways were identified, but few consistent PGx markers emerged. Extensive, unbiased studies with diverse populations are crucial to advancing the field.

REGISTRATION: A protocol was pre-registered at PROSPERO under registration number CRD42022296097.

DATA DEPOSITION: Data sets generated by this review are available at figshare: DOI: 10.6084/m9.figshare.27959616.

PMID:40116580 | DOI:10.1080/14622416.2025.2481025

World J Exp Med. 2025 Mar 20;15(1):97404. doi: 10.5493/wjem.v15.i1.97404. eCollection 2025 Mar 20.

ABSTRACT

Inflammatory bowel disease (IBD) represents a significant disease burden marked by chronic inflammation and complications that adversely affect patients' quality of life. Effective diagnostic strategies involve clinical assessments, endoscopic evaluations, imaging studies, and biomarker testing, where early diagnosis is essential for effective management and prevention of long-term complications, highlighting the need for continual advancements in diagnostic methods. The intricate interplay between genetic factors and the outcomes of biological therapy is of critical importance. Unraveling the genetic determinants that influence responses and failures to biological therapy holds significant promise for optimizing treatment strategies for patients with IBD on biologics. Through an in-depth examination of current literature, this review article synthesizes critical genetic markers associated with therapeutic efficacy and resistance in IBD. Understanding these genetic actors paves the way for personalized approaches, informing clinicians on predicting, tailoring, and enhancing the effectiveness of biological therapies for improved outcomes in patients with IBD.

PMID:40115750 | PMC:PMC11718585 | DOI:10.5493/wjem.v15.i1.97404

Blood Sci. 2025 Mar 19;7(2):e00227. doi: 10.1097/BS9.0000000000000227. eCollection 2025 Jun.

ABSTRACT

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy characterized by poor clinical outcomes, frequently exacerbated by mutations in the FMS-like tyrosine kinase 3 (FLT3) gene. Although FLT3 inhibitors (FLT3i) have emerged as promising therapeutic agents, the absence of molecular biomarkers to predict FLT3i response remains a critical limitation in clinical practice. In this study, we performed a comprehensive multi-omics analysis integrating transcriptomic, proteomic, and pharmacogenomic data from the Beat AML cohort, the Cancer Cell Line Encyclopedia (CCLE), and the PXD023201 repository to elucidate the molecular consequences of FLT3 mutations in AML. Our analysis revealed significant differences in RNA and protein expression profiles between FLT3-mutant and wild-type AML cases, with a particularly striking association between FLT3 mutations and immune suppression. We further evaluated the drug sensitivity of FLT3-mutant patients to 3 FDA-approved FLT3i, gilteritinib, midostaurin, and quizartinib, and observed heightened sensitivity in FLT3-mutant cohorts, accompanied by the activation of immune-related pathways in treatment-responsive groups. These findings suggest a potential synergy between FLT3i efficacy and immune activation. Through rigorous bioinformatic analysis, we identified 3 candidate biomarkers: CD36, SASH1, and NIBAN2, associated with FLT3i sensitivity. These biomarkers were consistently upregulated in favorable prognostic subgroups and demonstrated strong correlations with immune activation pathways. The identification of CD36, SASH1, and NIBAN2 as predictive biomarkers offers a novel toolset for stratifying FLT3i response and prognosis.

PMID:40115132 | PMC:PMC11925420 | DOI:10.1097/BS9.0000000000000227

Pharmacogenomics. 2025 Mar 21:1-7. doi: 10.1080/14622416.2025.2481015. Online ahead of print.

ABSTRACT

INTRODUCTION: Genetic variants can impact medication response. The study of genetic variants on medications is called pharmacogenomics (PGx). Understanding PGx results can be difficult as results are reported differently than other laboratory tests. Patients have reported a lack of understanding and satisfaction with PGx information.

METHODS: Surveys were emailed to patients seen in the PGx clinic and patients who participated in an elective screening (Sanford Chip) at Sanford Health. Surveys were conducted to assess literacy, understanding and satisfaction of PGx testing. Survey responses were summarized using descriptive statistics.

RESULTS: There were 121 responses that were initially collected. A total of 100 responses were included in the analysis. The median response amongst all individuals was 9 out of a possible 13 points on the PGx literacy assessment. PGx clinic patients had increased satisfaction compared to Sanford Chip patients for being able to understand results (p < 0.05), that PGx test provided information to improve my care plan (p < 0.05), that they feel confident that my medication will be effective for me based on my genetics (p < 0.05), were satisfied with communication of results (p < 0.001) and overall experience (p < 0.01).

DISCUSSION: Implementation of a PGx clinic improves patient experience, confidence, and satisfaction.

PMID:40114635 | DOI:10.1080/14622416.2025.2481015

Gene. 2025 Mar 18:149421. doi: 10.1016/j.gene.2025.149421. Online ahead of print.

ABSTRACT

BACKGROUND: Pharmacogenomics is used to identify genetic factors that influence drug responses, thereby optimizing therapeutic outcomes and reducing adverse effects. The objective of this study is to identify pharmacogenomic variations and their clinical relevance to drug metabolism and toxicity within the Pumi population.

METHODS: Eighty-two genetic variants in 43 genes were genotyped in 200 unrelated Pumi individuals using the Agena MassARRAY Assay. Chi-square tests, adjusted for multiple comparisons with Bonferroni correction, were used to compare genotype frequency divergences between the Pumi population and 26 other populations. Population genetic structure diversity and pairwise F-statistics (Fst) were assessed across 27 populations using Structure v2.3.1 and Arlequin v3.5 software.

RESULTS: After Bonferroni correction, a number of single nucleotide variations (SNVs) exhibited significant differences in frequency between the Pumi population and other populations. The allele frequencies of ADH1A rs975833, ADH1B rs1229984, TPMT rs1142345, and CYP2A6 rs8192726 in the Pumi population were notably different from the East Asian population or the other 26 populations. PharmGKB data indicate that rs1229984, rs1142345, and rs8192726 are associated with the metabolic efficiency of acetaldehyde, mercaptopurine, and efavirenz, respectively. Additionally, the genetic structure analysis (K = 5) and pairwise Fst calculations revealed that the Pumi population shared a similar genetic background with CHB (Fst = 0.031), JPT (Fst = 0.033), KHV (Fst = 0.035), CHS (Fst = 0.036), and CDX (Fst = 0.037) populations.

CONCLUSION: Our findings reveal unique genetic variations and biomarkers within the Pumi population, which contributes pharmacogenomic insights and theoretical foundations for personalized medicine tailored to the Pumi population.

PMID:40113188 | DOI:10.1016/j.gene.2025.149421

Pharmacogenomics. 2025 Mar 20:1-13. doi: 10.1080/14622416.2025.2481016. Online ahead of print.

ABSTRACT

AIM: To assess patient perspectives following evaluation in a multidisciplinary pharmacogenomics clinic run by a clinical pharmacist, genetic counselor, and physician.

METHODS: A survey was distributed to 187 adults seen in the Brigham and Women's Hospital Pharmacogenomics Clinic. Participants who completed the survey were invited to complete a semi-structured interview. Interview subjects were selected based on order of responses, scheduling availability, and range of participant experiences with testing and the clinic process. Surveys were analyzed with descriptive statistics, and interview transcripts were analyzed with thematic analysis.

RESULTS: Forty-two survey responses were received; 13 participants were interviewed. Quantitative data demonstrated high satisfaction with the multidisciplinary clinic model and belief that pharmacogenomic testing has value. Qualitative analysis identified four themes: 1) Self-Advocacy as a Patient Responsibility in the Utilization of Pharmacogenomic Results, 2) High Satisfaction with Multidisciplinary Pharmacogenomics Clinic Model and Team, 3) Utility of Pharmacogenomics, and 4) Desire for Pharmacogenomics Resources.

CONCLUSION: Patients value the care provided by a multidisciplinary pharmacogenomics clinic team, but they need to advocate for the use of their results with other healthcare professionals.

PMID:40111244 | DOI:10.1080/14622416.2025.2481016

Precis Clin Med. 2025 Feb 22;8(1):pbaf004. doi: 10.1093/pcmedi/pbaf004. eCollection 2025 Mar.

ABSTRACT

Pharmacogenomics, therapeutic drug monitoring, and the assessments of hepatic and renal function have made significant contributions to the advancement of individualized medicine. However, their lack of direct correlation with protein abundance/non-genetic factors, target drug concentration, and drug metabolism/excretion significantly limits their application in precision drug therapy. The primary task of precision medicine is to accurately determine drug dosage, which depends on a precise assessment of the ability to handle drugs in vivo, and drug metabolizing enzymes and transporters are critical determinants of drug disposition in the body. Therefore, accurately evaluating the functions of these enzymes and transporters is key to assessing the capacity to handle drugs and predicting drug concentrations in target organs. Recent advancements in the evaluation of enzyme and transporter functions using exogenous probes and endogenous biomarkers show promise in advancing personalized medicine. This article aims to provide a comprehensive overview of the latest research on markers used for the functional evaluation of drug-metabolizing enzymes and transporters. It also explores the application of marker omics in systematically assessing their functions, thereby laying a foundation for advancing precision pharmacotherapy.

PMID:40110576 | PMC:PMC11920622 | DOI:10.1093/pcmedi/pbaf004

Front Med (Lausanne). 2025 Mar 5;12:1476685. doi: 10.3389/fmed.2025.1476685. eCollection 2025.

ABSTRACT

The incidence of skin cancer continues to rise due to increased sun exposure and tanning habits, requiring early detection and treatment for favorable outcomes. Skin biopsy is an important diagnostic tool in dermatology and pathology, as it provides a valuable understanding of various skin diseases. Proper handling of skin biopsy specimens is vital to ensure accurate histopathological assessment. Still, the use of light microscopy and immunofluorescence provides a comprehensive approach to evaluating skin biopsy specimens, with each contributing unique information to aid in accurate diagnosis and management. This review highlights the evolution of skin biopsy practices, from traditional techniques to advanced methods incorporating artificial intelligence (AI) and convolutional neural networks. AI technologies enhance diagnostic accuracy and efficiency, aiding in the rapid analysis of skin lesions and biopsies. Despite challenges such as the need for extensively annotated datasets and ethical considerations, AI shows promise in dermatological diagnostics. The future of skin biopsy lies in minimally invasive techniques, liquid biopsies, and integrated pharmacogenomics for personalized medicine.

PMID:40109731 | PMC:PMC11919677 | DOI:10.3389/fmed.2025.1476685