Pharmacogenomics And Personalized Medicine[JOURNAL]
Sun
200 papers
Population-Based Assessment of Phenoconversion Potential in Switzerland: A Claims Data Study of Key Drug-Metabolizing Enzymes and Transporters.
Roth MM, Bencastro A, Meier CR … +4 more , Huber CA, Meyer Zu Schwabedissen HE, Allemann SS, Schneider C
Pharmgenomics Pers Med · 2026 · PMID 42199867 · Full text
PURPOSE: Drug-drug-gene interactions can alter drug exposure and thereby increase the risk of clinically relevant outcomes, such as concentration-dependent toxicity (eg, tacrolimus toxicity in the context of altered CYP3...
PURPOSE: Drug-drug-gene interactions can alter drug exposure and thereby increase the risk of clinically relevant outcomes, such as concentration-dependent toxicity (eg, tacrolimus toxicity in the context of altered CYP3A4/5 activity) or reduced treatment effectiveness. Despite their emerging relevance in clinical research, drug-drug-gene interactions remain understudied and are often ignored in clinical practice. Our objective was to assess the risk of phenoconversion by identifying potential drug-drug-gene interactions involving the transporters OATP1B1 and BCRP and the enzymes CYP2B6 and CYP3A4/5 in the Swiss population. PATIENTS AND METHODS: Using claims data from the Helsana basic health insurance, we identified all persons of all ages with at least one drug claim between 2017 and 2021 and with Helsana basic health insurance coverage for at least one full year. For the five-year analysis, only persons with insurance for the entire five-year period were included. Within this study population, we assessed and ranked the frequency of potential drug-drug-gene interactions of a pharmacogenetic substrate and an inhibitor/inducer of OATP1B1, BCRP, CYP2B6, or CYP3A4/5. Potential drug-drug-gene interactions were defined as the co-occurrence of a pharmacogenetic substrate and an inhibitor/inducer within a 30- or 5-days window. RESULTS: During the entire five-year period, 18'523 (2.1%) and 12'645 (1.4%) individuals were exposed to potential drug-drug-gene interactions using the 30-day and 5-day windows, respectively. Potential drug-drug-gene interactions most frequently involved CYP3A4/5 (81.0% and 85.3%), followed by CYP2B6 (10.9% and 8.7%) and OATP1B1 (8.7% and 13.3%). The top three drug classes involved were nervous system drugs (75.1%), cardiovascular drugs (10.6%), and dermatologicals (4.0%). Quetiapine ranked first in the number of involved drug pairs, with quetiapine - metamizole being the predominant drug pair. CONCLUSION: In Switzerland, two out of 100 persons taking drugs metabolized or transported by OATP1B1, BCRP, CYP2B6, and CYP3A4/5 are at potential risk of phenoconversion, predominantly involving CYP3A4/5. These findings quantify real-world phenoconversion potential at the population level and underscore the need for outcome- and genotype-linked studies to determine clinical relevance. As this study was not designed to assess clinical outcomes, future genotype- and outcome-linked investigations are required to determine the actual impact on adverse drug reactions or treatment effectiveness.
Massive Hepatocellular Carcinoma with Insufficient Future Liver Remnant Achieved Complete Response After Two-Stage Hepatectomy Combined with Hepatic Arterial Infusion Chemotherapy and Lenvatinib-sintilimab: A Case Report.
Xu R, Zhang M, Zeng Z … +5 more , Wei Y, Liao X, Yang C, Peng T, Su H
Pharmgenomics Pers Med · 2026 · PMID 41969849 · Full text
Massive hepatocellular carcinoma (HCC) is not suitable for radical surgery due to the factors of high tumor burden and poor postoperative liver function tolerance. There are few reports on the conversion therapy for HCC...
Massive hepatocellular carcinoma (HCC) is not suitable for radical surgery due to the factors of high tumor burden and poor postoperative liver function tolerance. There are few reports on the conversion therapy for HCC with insufficient future liver remnant (FLR) volume using a combination of two - stage hepatectomy (TSH), hepatic arterial infusion chemotherapy (HAIC), and lenvatinib - sintilimab. We report a case of a 62-year-old male with massive HCC (81mm×11.5mm×95mm). At the initial diagnosis, the ratio of his FLR to standard liver volume (SLV) was 34%. After multidisciplinary team (MDT) discussion, the patient decided to undergo conversion therapy. After three formal cycles (9 weeks) of conversion therapy, the FLR/SLV ratio increased to 65%, and then right hepatectomy was performed. The lesion achieved a partial response (PR) according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. The second hepatectomy was successfully performed, and there was no recurrence during the 36-month postoperative follow-up. In this case, portal vein ligation (PVL) surgery, HAIC, and targeted immunotherapy contributed to the conversion therapy of HCC through different dimensions, including mechanical blood flow blockage, local chemotherapy, and immune regulation, laying the foundation for the safety of radical surgery and long-term postoperative survival.
Construction and Validation of Multi-Omics Predictive Models for Colorectal Cancer Using Machine-Learning Approaches.
Lu Z, Li X, Liang Z … +5 more , Zhang X, Tan Y, Kuang Y, Li K, Zhu X
Pharmgenomics Pers Med · 2026 · PMID 41947871 · Full text
OBJECTIVE: To construct and externally validate a multi-omics nomogram that uses only routine clinicopathological variables to predict tumor mutational burden (TMB), microsatellite instability (MSI), NTRK/PIK3CA mutation...
OBJECTIVE: To construct and externally validate a multi-omics nomogram that uses only routine clinicopathological variables to predict tumor mutational burden (TMB), microsatellite instability (MSI), NTRK/PIK3CA mutation status and overall survival (OS) in colorectal cancer (CRC). METHODS: TCGA data (n=398) served as the training set and 120 consecutive CRC patients who underwent radical resection at Yuebei People's Hospital formed the prospective validation set. After z-score normalization, 21demographic, clinical and pathological features were screened for multicollinearity (VIF<5) and redundancy via least absolute shrinkage and selection operator (LASSO) regression with 10-fold cross-validation. Optimal hyper-parameters for each algorithm were tuned by nested 10-fold grid search. Four machine-learning algorithms, logistic regression (LR), support-vector machine (SVM), decision tree (DT) and random forest (RF), were compared by area under the receiver-operating-characteristic curve (AUC), F1 score and decision-curve analysis. The best model was externally validated and calibrated with bootstrapping. RESULTS: The results showed that the TMB prediction model included in the MSI index had the best power when constructed by the RF method, with an area under the ROC curve value of 0.9597. For the MSI state prediction model which includes three indicators of TMB, had the best power when constructed by RF method, with AUC value of 0.8225. The and gene status prediction model, which included three indicators of TMB and MSI status, had the best power when constructed using the RF method. CONCLUSION: The prediction model constructed in this study can help clinicians quickly identify high-risk patients and provide a basis for formulating a reasonable treatment plan. Further optimization of the model and expansion of the sample size are required to verify its power in the future.
Clinical Outcomes of Osimertinib Combined with Platinum-Based Chemotherapy in EGFR-Mutant Non-Small Cell Lung Cancer: A Retrospective Study.
Han R, Yu X
Pharmgenomics Pers Med · 2026 · PMID 41908738 · Full text
OBJECTIVE: To assess the clinical outcomes of osimertinib combined with platinum-based chemotherapy in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) and to describe assoc...
OBJECTIVE: To assess the clinical outcomes of osimertinib combined with platinum-based chemotherapy in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) and to describe associated changes in angiogenesis-related and tumor marker levels. METHODS: A retrospective analysis was performed on 112 NSCLC patients with EGFR-sensitive mutations treated from June 2018 to October 2020. Patients received either pemetrexed plus cisplatin (control group, n=56) or the same regimen with osimertinib (experimental group, n=56). Evaluation parameters included objective response rate (ORR), disease control rate (DCR), vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2), carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA21-1), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events. RESULTS: ORR was comparable between groups (P>0.05), whereas the experimental group showed a significantly higher DCR (P<0.05). Post-treatment VEGF, Ang-2, CEA, and CYFRA21-1 levels decreased in both groups, with greater reductions observed in the experimental group (P<0.05). Median follow-up was 18.8 months. The experimental group demonstrated longer median PFS (15.7 vs 10.6 months, χ=18.337, P<0.001) and OS (24.6 vs 17.5 months, χ=24.679, P<0.001). The incidence of adverse reactions did not differ significantly between groups (P>0.05). CONCLUSION: In this retrospective cohort, the addition of osimertinib to platinum-based chemotherapy was associated with improved disease control and prolonged survival, along with greater reductions in angiogenesis-related and tumor marker levels, without increasing treatment-related toxicity.
Post-Translational Modifications of Histones and Non-Histones in Liver Disease and Traditional Chinese Medicine Treatment: A Narrative Review.
Xie Z, Deng Y, Zhang X … +5 more , Chen J, Deng J, Fang Y, Ye X, Zhou Z
Pharmgenomics Pers Med · 2026 · PMID 41908737 · Full text
Post-translational modifications (PTMs) of histones and non-histones are significant epigenetic modifications in humans, including acetylation, methylation, phosphorylation, glycosylation, and ubiquitination. These modif...
Post-translational modifications (PTMs) of histones and non-histones are significant epigenetic modifications in humans, including acetylation, methylation, phosphorylation, glycosylation, and ubiquitination. These modifications regulate chromatin structure and gene expression, enabling proteins to perform their normal biological functions within cells and maintain stable expression. It is also closely related to the development process of liver diseases and plays an important role in the pathological processes of liver cancer, liver fibrosis, alcoholic fatty liver disease and non-alcoholic fatty liver disease. This article reviews the roles and pathway mechanisms mediated by post-translational modifications of histones and non-histones in these liver diseases, and briefly outlines how traditional Chinese medicine (TCM) can intervene in liver diseases by modulating protein post-translational modifications, providing new strategies for future prevention and treatment of liver diseases.
NAT2 Acetylation Phenotypes in India: A Narrative Review of Personalized TB Therapy.
Khan N, Jonnalagadda M, Kumar R … +1 more , Das A
Pharmgenomics Pers Med · 2026 · PMID 41836751 · Full text
Tuberculosis (TB) continues to be a significant health challenge in India, which necessitates accurate and personalized therapeutic strategies for its successful treatment. Polymorphisms in the N-acetyltransferase-2 () e...
Tuberculosis (TB) continues to be a significant health challenge in India, which necessitates accurate and personalized therapeutic strategies for its successful treatment. Polymorphisms in the N-acetyltransferase-2 () enzyme, involved in metabolism of a first-line drug, isoniazid (INH), for treatment of TB, have three acetylation phenotypes (slow, intermediate, or fast) that influence drug efficacy, toxicity and treatment outcomes. This article is presented as a narrative review of current research retrieved from PubMed, Scopus, and Google Scholar, focusing on studies related to polymorphisms, pharmacogenomics, and tuberculosis therapy. The selected literature was reviewed to address the biological importance of the acetylation process and the development of DNA-based methods for genotyping of the gene and discussion of their clinical applications, as well as the effect of phenotypes on the treatment outcomes of TB. In addition, how highly genetic diversity in Indian populations necessitates the development of simplified and personalized medication therapy using population-based phenotyping approaches is discussed. The need for nationwide mapping of variants and the deployment of rapid, cost-effective genotyping platforms, especially in resource-limited endemic settings, are also emphasized. Moreover, how combining profiling with additional pharmacogenetic markers may lead to a comprehensive framework for TB treatment optimization is also discussed. It is envisioned that integration of all of these approaches under -guided therapy in India's National TB Elimination Programme (NTEP) might change the dynamics of TB management in India.
Bioinformatic Identification and Preliminary Validation of TP53, TGFB1, and NFE2L2 as Potential Ferroptosis-Related Regulators in Pancreatic Adenocarcinoma.
Li S, Zhang C, Lv S … +3 more , Zhang Z, Xu D, Xu T
Pharmgenomics Pers Med · 2026 · PMID 41737899 · Full text
BACKGROUND: Pancreatic adenocarcinoma (PAAD) is a highly malignant tumor with very poor prognosis for patients. Ferroptosis, as a novel cell death mechanism, brings a new direction for PAAD therapeutic research. METHODS:...
BACKGROUND: Pancreatic adenocarcinoma (PAAD) is a highly malignant tumor with very poor prognosis for patients. Ferroptosis, as a novel cell death mechanism, brings a new direction for PAAD therapeutic research. METHODS: Ferroptosis-related differentially expressed genes were identified by bioinformatic analysis of the FerrDb, TCGA, and GTEx databases. A series of analyses, including functional enrichment, protein-protein interaction (PPI) networking, survival analysis, and immune infiltration profiling, were performed to screen for and characterize hub genes. Subsequently, the expression of key hubs-NFE2L2 (NRF2), TGFB1, and TP53-was validated in PDAC patient tissues and cell lines using qRT-PCR and Western blot. Their biological functions were investigated via shRNA-mediated knockdown in BxPC-3 cells, followed by assays for cell migration (wound healing, transwell) and ferroptosis (ROS, MDA, GSH/GSSG). RESULTS: Bioinformatic analysis identified 221 ferroptosis-related DEGs. NFE2L2, TGFB1, and TP53 emerged as core hub genes whose high expression correlated with poor patient survival and specific immune infiltration patterns. Experimental validation confirmed that NRF2, TGFβ1, and TP53 proteins were significantly upregulated in PDAC tissues compared to adjacent normal tissues. Functionally, knockdown of NFE2L2 and TGFB1 suppressed PDAC cell migration, whereas TP53 knockdown enhanced it. Inversely, NFE2L2 knockdown promoted ferroptosis (increased ROS and MDA, decreased GSH), while knockdown of both TGFB1 and TP53 inhibited ferroptosis. CONCLUSION: TP53, TGFB1, and NRF2 are key ferroptosis-related regulators in PAAD, influencing tumor progression, ferroptosis sensitivity, and immune contexture. These findings provide new insights and potential targets for ferroptosis-based therapies in PAAD.
Managing Refractory Hypertension: A Case Study Exploring the Influence of ACE and ACTN3 Gene Polymorphisms.
Gasser B, Dössegger A, Flück M
Pharmgenomics Pers Med · 2025 · PMID 41450759 · Full text
The responses to Antihypertensive drugs vary among patients. The renal and muscular processes of blood flow regulation in peripheral blood vessels depend on the genetic and physiological constitution. Here, we present a...
The responses to Antihypertensive drugs vary among patients. The renal and muscular processes of blood flow regulation in peripheral blood vessels depend on the genetic and physiological constitution. Here, we present a case of an elderly female patient who experienced several phases of hypertensive emergencies during supervised training sessions. Hypertension treatment with different ACE inhibitors was discontinued because of severe side effects or simply no effect. Genotyping of ACE and ACTN3 gene polymorphisms helped find adequate antihypertensive treatment after all other approaches failed. The measured ACTN3-RR genotype indicated the possibility of a higher proportion of fast-twitch muscle fibers. This type of muscle fiber contributes to the generation of a high muscle force, which can compress the vascular bed more during physical work than slow muscle fibers. Therefore, a beta-blocker was used for treatment, allowing better vasodilative capacity. As reported by the patient, this pharmaceutical alone helped treat hypertensive emergencies adequately. Therefore, we believe that genetic information can help to identify optimal pharmaceutical treatments a problem that is highly prevalent in elderly subjects.
Case Report: Successful Surgical Resection of PVTT Vp4 Hepatocellular Carcinoma Following Hepatic Arterial Infusion Chemotherapy Combined with Cadonilimab Plus Donafenib.
Chen S, Wei Y, Liao X … +5 more , Yang C, Zhu G, Han C, Su H, Peng T
Pharmgenomics Pers Med · 2025 · PMID 41383565 · Full text
OBJECTIVE: To evaluate the potential and efficacy of hepatic artery infusion chemotherapy combined with the PD-1/CTLA-4 bispecific antibody cadonilimab and the multi-kinase inhibitor donafenib in conversion therapy for u...
OBJECTIVE: To evaluate the potential and efficacy of hepatic artery infusion chemotherapy combined with the PD-1/CTLA-4 bispecific antibody cadonilimab and the multi-kinase inhibitor donafenib in conversion therapy for unresectable hepatocellular carcinoma (uHCC) with Vp4-type portal vein tumor thrombus(PVTT). METHODS: We present a case report of a 41-year-old male diagnosed with diffuse hepatocellular carcinoma (HCC) in the right lobe of the liver and tumor thrombus involving the main portal vein. Following multidisciplinary team evaluation, the patient received conversion therapy consisting of hepatic artery infusion chemotherapy (HAIC) using oxaliplatin, fluorouracil, and leucovorin, in combination with cadonilimab and donafenib. RESULTS: Post-treatment imaging demonstrated marked regression of intrahepatic tumors and complete resolution of the portal vein tumor thrombus. Serum alpha-fetoprotein (AFP) levels normalized, and protein induced by vitamin K absence or antagonist-II (PIVKA-II) levels showed a significant decline. Subsequently, a radical right hepatectomy was successfully performed, and postoperative pathological examination confirmed complete response. The patient experienced an uneventful recovery and remained free of tumor recurrence during the one-year follow-up period. CONCLUSION: The integrative treatment strategy combining HAIC with cadonilimab and donafenib demonstrates considerable promise as a conversion approach for patients with traditionally unresectable HCC with Vp4-type PVTT. This regimen may substantially improve oncological outcomes and enable curative resection. This case provides compelling evidence to support further clinical investigation of this multimodal therapeutic combination.
Berberine Repairs Intestinal Mucosal Barrier by Targeting HSP90AA1 and MAPK14.
Zhao D, Zhai Y, Chen C … +7 more , Chen J, Chen D, Yang Q, Yu Z, Shao S, Huang Y, Shu J
Pharmgenomics Pers Med · 2025 · PMID 41280249 · Full text
BACKGROUND: Berberine (BBR), a key compound in Coptis chinensis, has broad pharmacological properties, though its specific Crohn's disease (CD) targets and mechanisms are undefined. MATERIALS AND METHODS: We employed net...
BACKGROUND: Berberine (BBR), a key compound in Coptis chinensis, has broad pharmacological properties, though its specific Crohn's disease (CD) targets and mechanisms are undefined. MATERIALS AND METHODS: We employed network pharmacology, mendelian randomization (MR), molecular docking, and molecular dynamics simulations to identify potential target genes. Next, we assessed the efficacy of BBR in vitro and in vivo. RESULTS: HSP90AA1 and MAPK14 were identified as potential target genes of BBR in the treatment of CD. In vitro experiments revealed that BBR downregulated LPS-induced HSP90AA1, MAPK14, and TNF-α while restoring tight junction proteins (ZO-1, Occludin, Claudin-1, JAM-A). Both HSP90AA1 inhibitor (17-AAG) and MAPK14 inhibitor (SB203580) significantly mitigated the reduction in ZO-1, Occludin, Claudin-1, and JAM-A expression caused by LPS. Furthermore, in vivo experiments revealed that BBR treatment effectively alleviated weight loss, the disease activity index (DAI), and colon shortening in a model of DSS-treated mice. BBR also ameliorated pathological changes in the colon, repaired goblet cells, reduced the expression of HSP90AA1, MAPK14, and TNF-α, and increased the expression of ZO-1, Occludin, Claudin-1, and JAM-A. CONCLUSION: BBR inhibits the expression of HSP90AA1 and MAPK14 both in vitro and in vivo, thereby facilitating the repair of the intestinal mucosal barrier.
Genetic Landscape of VIP Pharmacogenomic Variants in the Kinh Vietnamese Population.
Tong H, Phan VTN, Nguyen T … +1 more , Le L
Pharmgenomics Pers Med · 2025 · PMID 41112219 · Full text
BACKGROUND: Genetic polymorphisms in the genes encoding enzymes and proteins in drug metabolism, transport, and response can significantly impact enzymatic activity and overall pharmacokinetics and pharmacodynamics, lead...
BACKGROUND: Genetic polymorphisms in the genes encoding enzymes and proteins in drug metabolism, transport, and response can significantly impact enzymatic activity and overall pharmacokinetics and pharmacodynamics, leading to inter-individual and inter-population differences in drug efficacy and safety. The prevalence of pharmacogenomic variants often differs among populations due to unique evolutionary and demographic factors. By studying the genetic variation within 100 pharmacogenes in the Kinh Vietnamese population, a relatively underexplored group in pharmacogenomic research, we aim to provide insights into the population-specific pharmacogenomic landscape. MATERIALS AND METHODS: 100 healthy people were recruited for peripheral blood donation after getting consents. Genomic DNA from participants was sequenced at coding regions of 100 pharmacogenes. Sequence reads were qualified, and variants were called using Genome analysis toolkit (GATK) followed with variant processing. Very important variants were characterized. Genetic distance using pairwise fixation index and allele frequencies comparison between the Kinh population and 25 populations of the 1000 Genome Project were analyzed. RESULTS: 689 variants were called with 652 SNPs and 37 indels including 371 missense-, 266 synonymous-, 30 frameshift-, 14 stop-gain-, 2 stop-lost-, 3 in-frame insertion-, 2 in-frame deletion- and 1 protein variant. There are 59 novel variants (8.6%) present in 39/100 genes in which 13 variants are labeled with damaging phenotype. 28 VIP variants were obtained from these regions. Allele frequencies of variants are mostly similar with East Asians, but different from Africans. Remarkably, variants rs1801280 and rs1208 (NAT2), rs2231142 (ABCG2), rs2306283 (SCLO1B1) and rs4148323 (UGT1A1) distribute significantly between Kinh people and all other populations. CONCLUSION: The prevalence of pharmacogenomic variants of 100 pharmacogenes was obtained for Kinh Vietnamese people, in which 28 variants were characterized as very important variants. Kinh Vietnamese shows close genetic distance with East Asians but far from Africans. The variants with distinguished distribution in Kinh people were also highlighted.
Whole Exome Sequencing Reveals Novel Genetic Variants Associated with Atrial Septal Defect in a Tibetan Patient Cohort.
Li H, He Y, Cai Z … +5 more , Che Q, Wu Y, Zhou M, He Z, Zhao L
Pharmgenomics Pers Med · 2025 · PMID 40955363 · Full text
OBJECTIVE: Atrial septal defect (ASD) is a common congenital heart defect with incompletely understood genetic underpinnings, particularly in specific ethnic groups. This study aimed to identify novel genetic variants re...
OBJECTIVE: Atrial septal defect (ASD) is a common congenital heart defect with incompletely understood genetic underpinnings, particularly in specific ethnic groups. This study aimed to identify novel genetic variants related to ASD within the Tibetan population using whole exome sequencing (WES). METHODS: Genomic DNA was extracted from blood samples of 17 Tibetan ASD patients. WES was performed using the Illumina HiSeq platform. After rigorous filtering, detection, and annotation of single nucleotide variations (SNVs) and insertion-deletions (InDels), potentially pathogenic variants were prioritized. Functional impact predictions were conducted using SIFT, PolyPhen V2, MutationTaster, and CADD databases to identify variants likely contributing to ASD etiology. RESULTS: We identified nine high-confidence candidate variants in Tibetan ASD patients, including rs145116532 (, c.287G >A: p. R96Q), rs374798430 (, c.1267G >A: p.D423N), rs138933092 (, c.4432C >T: p.R1478W), rs141638421 (, c.470G>A: p.R157H), rs147287319 (, c.989G>A: c.1193G>A: p.R330Q, p.R398Q), rs141616597 (, c.1243C>T: p.R415C), rs117506395 (, c.2207C>T: p.T736M), rs142533677 (, c.2246G>A: p.R749Q), and rs118203532 (, c.1460C>G: p.S487C). Function annotation further suggested potential associations of , and with congenital heart diseases. CONCLUSION: This first WES-based study of Tibetan ASD patients reveals population-specific genetic determinants. The nine novel candidate variants, particularly in , and , provide preliminary insights into ASD etiology in high-altitude populations and highlight potential targets for future diagnostic biomarker development.
Ulcerative Colitis: Advances in Pathogenesis, Biomarkers, and Therapeutic Strategies.
Bu S, Cheng X, Chen M … +1 more , Yu Y
Pharmgenomics Pers Med · 2025 · PMID 40937422 · Full text
Ulcerative colitis represents an inflammatory bowel disease with multiple contributing factors, marked by persistent inflammation of the colonic mucosa, which can lead to a reduced life expectancy and an elevated likelih...
Ulcerative colitis represents an inflammatory bowel disease with multiple contributing factors, marked by persistent inflammation of the colonic mucosa, which can lead to a reduced life expectancy and an elevated likelihood of requiring colectomy as well as developing colorectal cancer. Despite impacting roughly 5 million individuals worldwide, the intricate mechanisms underlying ulcerative colitis are still inadequately defined, hindering the development of effective treatments. Extra-intestinal complications, including enteropathic arthritis, are also addressed in the context of disease burden and management. This review explores the multifaceted pathogenesis of ulcerative colitis, emphasizing critical factors such as abnormalities in the epithelial barrier, irregular immune responses, the release of inflammatory mediators, and alterations in gut microbiota composition. We also underscore recent advancements in diagnostic biomarkers that improve the accuracy of disease detection and monitoring. Conventional medicinal strategies are reviewed alongside the emergence of biological therapies, notably those that target tumor necrosis factor (TNF), interleukins, and integrins, which have significantly altered management approaches. Established therapies (eg, 5-aminosalicylic acid, corticosteroids) and emerging agents (eg, JAK inhibitors, S1P modulators) are clearly delineated. Combination strategies-such as dual biologic regimens or JAK inhibitors combined with anti-integrin agents-are also discussed in dedicated subsections. We discuss novel therapies that utilize small molecule targeting, particularly those that inhibit Janus kinase (JAK) and modulate sphingosine-1-phosphate (S1P) receptors, presenting promising avenues for treatment. Additionally, fecal microbiota transplantation (FMT) is evaluated as a therapeutic option, as it shows promise in restoring microbial balance. Collectively, these advances underscore the pivotal roles of immune dysregulation, biologic therapies, and microbiota modulation in reshaping precision management of ulcerative colitis. This synthesis of current knowledge underscores the necessity for continued research to refine therapeutic strategies and improve patient outcomes in ulcerative colitis.
The Prevalence of Potential Drug-Drug-Gene Interactions: A Descriptive Study Using Swiss Claims Data.
Wittwer NL, Meier CR, Huber CA … +4 more , Moser JD, Meyer Zu Schwabedissen HE, Allemann SS, Schneider C
Pharmgenomics Pers Med · 2025 · PMID 40895400 · Full text
PURPOSE: We aimed to determine the prevalence of interactions between PGx drugs metabolized by CYP2C9, CYP2C19, and CYP2D6 and drugs that act as inhibitors or inducers of those enzymes in the Swiss population. PATIENTS A...
PURPOSE: We aimed to determine the prevalence of interactions between PGx drugs metabolized by CYP2C9, CYP2C19, and CYP2D6 and drugs that act as inhibitors or inducers of those enzymes in the Swiss population. PATIENTS AND METHODS: We defined concomitant use of PGx drugs and inhibitors/inducers as instances where a claim of a PGx drug and a claim of an inducer or inhibitor concerning the same enzyme were made within a specified temporal window, either ± 5 days or ± 30 days. We assessed concomitant drug use between 2017 and 2021, using claims data from a Swiss insurance company (Helsana). RESULTS: Out of 894,748 individuals continuously insured, between 17.4% (± 5-days window) and 24.8% (± 30-days window) were exposed to potentially interacting drug pairs, with 1.5% to 2.2% being exposed to potentially strong interacting drug pairs. Individuals exposed to potentially interacting drugs were more frequently female, older and took a greater number of drugs than the general population. The majority of potential interactions were associated with CYP2D6 or CYP2C19. CONCLUSION: In light of the high prevalence of the simultaneous use of PGx drugs with inhibitor and inducer drugs, it is imperative to consider non-genetic factors, such as drug-induced phenoconversions, when interpreting PGx test results.
Association Between ABCB1 Gene Polymorphism with Hyperglycemia and MACE in Patients Undergoing Clopidogrel Treatment After PCI.
Zhou B, Shi C, Xu Q … +4 more , Wei Y, Zhang S, Wang X, An X
Pharmgenomics Pers Med · 2025 · PMID 40895399 · Full text
PURPOSE: To evaluate the effect of C3435T gene polymorphism with hyperglycemia on the risk of major adverse cardiovascular events (MACE) in patients treated with clopidogrel after percutaneous coronary intervention (PCI...
PURPOSE: To evaluate the effect of C3435T gene polymorphism with hyperglycemia on the risk of major adverse cardiovascular events (MACE) in patients treated with clopidogrel after percutaneous coronary intervention (PCI). PATIENTS AND METHODS: A total of 117 patients were studied, of which 52 developed MACE. We used fluorescence in situ hybridization to detect the genotype of the and C3435T loci. Baseline characteristics, fasting blood glucose, and clinical outcomes were collected. Logistic regression was used to analyze factors influencing MACE in PCI patients treated with clopidogrel. RESULTS: There were significant differences between normal and MACE groups in gender, age, history of diabetes mellitus, history of alcohol consumption, fasting blood glucose, (CC) with normoglycemia, and (CT/TT) combined with hyperglycemia ( < 0.05). C3435T genotype (= 0.024, OR = 5.584, 95% CI 1.258-24.780), age (= 0.014, OR = 1.073, 95% CI 1.014-1.135), History of hypertension (= 0.020, OR = 3.144, 95% CI 1.200-8.238) and History of diabetes mellitus (= 0.030, OR = 3.731, 95% CI 1.135-12.270) were independent MACE risk factors. In patients <75 years, history of hypertension (= 0.021, OR = 3.151, 95% CI 1.189-8.350) was a risk factor, while the (CC) with normoglycaemia (= 0.023, OR = 0.147, 95% CI 0.028-0.767) was a protective factor. CONCLUSION: The C3435T genotype is an independent risk factor for MACE after PCI with clopidogrel therapy. CC combined normoglycemia may protect against MACE in patients <75 years. TRIAL REGISTRATION: Registration number: ChiCTR2400082012, Reg Date: 2024-03-19.
Dual EGFR L858R and KRAS G12A Mutations in Lung Adenocarcinoma: A Rare Case Report and Literature Review.
Wei G, Tang J, Wang H … +1 more , Zhang D
Pharmgenomics Pers Med · 2025 · PMID 40873627 · Full text
BACKGROUND: KRAS mutations are typically mutually exclusive in non-small cell lung cancer (NSCLC), with the G12C mutation being the most common subtype. The coexistence of KRAS and EGFR mutations is exceedingly rare and...
BACKGROUND: KRAS mutations are typically mutually exclusive in non-small cell lung cancer (NSCLC), with the G12C mutation being the most common subtype. The coexistence of KRAS and EGFR mutations is exceedingly rare and is typically emerges as a secondary event following acquired resistance to EGFR-targeted therapies. We presented a case of a newly diagnosed NSCLC patient harboring concurrent EGFR L858R and KRAS G12A mutations. CASE PRESENTATION: A 64-year-old male with a 30-pack-year smoking history presented with a 3-month history of progressive shortness of breath and chest tightness. Contrast-enhanced chest CT revealed a 5 cm spiculated mass in the right upper lobe, abutting the mediastinum, along with bronchial obstruction, right middle lobe atelectasis, and pleural effusion. A CT-guided transthoracic needle biopsy confirmed lung adenocarcinoma. Next-generation sequencing (NGS) identified a c.2573T>G (p.L858R) mutation in exon 21 of the EGFR gene and a c.35G>C (p.G12A) mutation in exon 2 of the KRAS gene. The patient started first-line therapy with osimertinib combined with pemetrexed/nedaplatin, resulting in a transient partial response, significant resolution of pleural effusion, and partial regression of the primary tumor. However, disease progression occurred within 6 months, marked by the appearance of a new cerebellar metastasis, confirmed by MRI. The patient continued osimertinib maintenance therapy and underwent stereotactic radiotherapy for the brain lesion. Despite initial stabilization, pulmonary progression was observed 11 months after the start of treatment. Due to declining performance status and personal preferences, the patient declined further treatment and was lost to follow-up. CONCLUSION: We report a rare case of treatment-naïve lung adenocarcinoma harboring concurrent KRAS G12A and EGFR L858R mutations. The patient achieved only transient disease control following treatment with a third-generation EGFR TKI combined with chemoradiotherapy. Further research to explore optimal therapeutic strategies for such complex molecular profiles is needed.
Construction of a Nomogram Model for Predicting Prognosis in Breast Cancer Patients Based on the Expression of THRSP and ACACA Proteins Tissues.
Wei B, Li F, Yan H … +1 more , Shen J
Pharmgenomics Pers Med · 2025 · PMID 40771877 · Full text
BACKGROUND: This study aimed to analyze the expression of thyroid hormone-responsive spot 14 (THRSP) and acetyl-CoA carboxylase alpha (ACACA) proteins in breast cancer tumor tissues and their relationship with clinicopat...
BACKGROUND: This study aimed to analyze the expression of thyroid hormone-responsive spot 14 (THRSP) and acetyl-CoA carboxylase alpha (ACACA) proteins in breast cancer tumor tissues and their relationship with clinicopathology and prognosis of breast cancer patients. In addition, a nomogram model to predict the prognosis of breast cancer patients was constructed in this study. METHODS: Retrospective analysis of 202 cases of breast cancer patients who underwent surgical treatment in our hospital from October 2019 to March 2021, and collection of patients' cancer tissues and non-Tumor tissue specimens. Immunohistochemistry was used to detect THRSP and ACACA protein expression. Multivariate COX regression was used to analyze the risk factors affecting the prognosis of breast cancer patients. The "rms" package in R software was used to build a survival nomogram model and evaluate the effectiveness of the model. RESULTS: The expression of THRSP and ACACA proteins in tumor tissues of breast cancer patients was higher than that in non-tumor tissues ( < 0.05). The expression of THRSP and ACACA proteins in breast cancer patients with lymph node metastasis was higher than that in patients without lymph node metastasis ( < 0.05). Cox regression analysis showed that TNM stage III, lymph node metastasis, high expression of Ki-67, high expression of THRSP, and high expression of ACACA were all risk factors for the prognosis of breast cancer patients ( < 0.05). The C-index of the nomogram model was 0.704 (95% CI: 0.596~0.892). The predicted 1-, 2- and 3-year survival AUCs of this nomogram model were 0.802, 0.769 and 0.770, respectively. The calibration curve showed that the model fit the ideal curve well. Decision curve analysis showed the high clinical utility of the model. CONCLUSION: The nomogram model constructed based on THRSP and ACACA proteins may provide a reference value for the prognostic evaluation of breast cancer patients.
Advances in the Clinical Use of Clopidogrel: A Review of Individualized Treatment Strategies and Monitoring Optimization Based on Genetic Polymorphisms.
Dou N, Ma H, Zhang P … +3 more , Lu R, Hang J, Sun J
Pharmgenomics Pers Med · 2025 · PMID 40661922 · Full text
This paper systematically reviews recent advances in clopidogrel clinical applications to optimize therapeutic precision and medication safety. Using a literature review methodology, we elucidate clopidogrel's pharmacoki...
This paper systematically reviews recent advances in clopidogrel clinical applications to optimize therapeutic precision and medication safety. Using a literature review methodology, we elucidate clopidogrel's pharmacokinetic properties and pharmacodynamic mechanisms, while evaluating its clinical efficacy and adverse reactions in disease management. Recent studies have emphasized the key role of genetic polymorphisms in regulating the efficacy and safety of clopidogrel. Polymorphisms in the gene have a significant effect on the metabolism of clopidogrel, with loss-of-function (LOF) alleles () reducing the production of active metabolites, leading to elevated platelet reactivity and increasing the risk of major adverse cardiovascular events (MACE), particularly in the Asian populations, where the prevalence of LoF alleles is as high as 29-35%. In contrast, the gain-of-function allele results in a reduced risk of cardiovascular events but increases the risk of bleeding. This article summarizes the latest research progress and monitoring methods of clopidogrel, and suggests that clinics should combine genotyping and platelet function testing with monitoring of blood levels to optimize treatment and provide data reference for clinical administration of clopidogrel.
Molecular Genetic Analysis of a Frameshift Mutation in a Boy with Duchenne Muscular Dystrophy by MLPA and Sanger Sequencing.
Chen Q, Zhang W, Zha L
Pharmgenomics Pers Med · 2025 · PMID 40548338 · Full text
Duchenne muscular dystrophy (DMD) is an X-linked recessive neuromuscular disease that is characterized by progressive proximal muscle weakness and pseudohypertrophy. Currently, genetic diagnosis of DMD relies largely on...
Duchenne muscular dystrophy (DMD) is an X-linked recessive neuromuscular disease that is characterized by progressive proximal muscle weakness and pseudohypertrophy. Currently, genetic diagnosis of DMD relies largely on multiplex ligation-dependent probe analysis (MLPA) and Sanger sequencing to identify pathogenic mutations. This study aimed to confirm the genetic etiology of a boy presenting with clinical manifestations that are highly indicative of DMD. A 14-year-old boy with heart failure and extreme muscle weakness along with his family members was recruited for this study. DNA from each participant was isolated from peripheral blood samples. We used MLPA to detect the deletion or duplication mutations of the gene and Sanger sequencing to verify the missing region of the exon in the proband. Furthermore, the functional role of the mutation was assessed using bioinformatics. We found that the proband carried a small deletion in the gene (c.6808_6811delTTAA). The deletion of those four nucleotides resulted in a frameshift mutation and a premature nonsense codon, which resulted in a truncated dystrophin that lost its most critical function and underwent post-transcriptional degradation. Our study demonstrated that MLPA, in combination with Sanger sequencing, is a reliable and practical approach for the genetic diagnosis of DMD, which is a significant step towards developing personalized therapy.
Associations Between Polymorphisms and Neuroblastoma Risk in Chinese Children.
Liu P, Li Y, Li Y … +9 more , Li L, Cheng J, Li S, Zhang J, Zhou H, Huo Y, Yang Z, He J, Zhang R
Pharmgenomics Pers Med · 2025 · PMID 40453563 · Full text
BACKGROUND: Neuroblastoma (NB) is a malignancy of neural crest cells that primarily affects children. Single nucleotide polymorphisms (SNPs) in the fat mass and obesity-associated () gene, a well-conserved gene, have bee...
BACKGROUND: Neuroblastoma (NB) is a malignancy of neural crest cells that primarily affects children. Single nucleotide polymorphisms (SNPs) in the fat mass and obesity-associated () gene, a well-conserved gene, have been implicated in tumorigenesis. However, there is currently insufficient evidence to establish the relationship between gene SNPs and susceptibility to NB. METHODS: A TaqMan assay was conducted to examine the potential associations between gene SNPs and the risk of NB in a cohort of 898 patients and 1734 controls from eight medical centers in China. Additionally, stratification analysis was performed to evaluate the relationship between the selected SNPs and the susceptibility to NB among various subgroups. RESULTS: No significant association was found between the selected polymorphisms and the risk of NB in either the single locus analysis or the combined analysis. CONCLUSION: However, our study reveals that individuals with retroperitoneal NB and those with stage III+IV NB are more prone to exhibit SNPs compared to other patients. Moreover, participants with the rs8047395 GG genotype displayed a higher likelihood of developing stage III+IV NB in comparison to other participants.
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