Pharmacogenomics and Personalized Medicine最新文献

{"title":"Pharmacogenomic Analysis of CYP3A5*3 and Tacrolimus Trough Concentrations in Vietnamese Renal Transplant Outcomes","authors":"Thi Van Anh Nguyen, Ba Hai Le, Minh Thanh Nguyen, Viet Thang Le, Viet Tien Tran, Dinh Tuan Le, Duong Anh Minh Vu, Quy Kien Truong, Trong Hieu Le, Huong Thi Lien Nguyen","doi":"10.2147/pgpm.s439400","DOIUrl":"https://doi.org/10.2147/pgpm.s439400","url":null,"abstract":"<strong>Purpose:</strong> CYP3A5 polymorphisms have been associated with variations in the pharmacokinetics of tacrolimus (Tac) in kidney transplant patients. Our study aims to quantify how the CYP3A5 genotype influences tacrolimus trough concentrations (C₀) in a Vietnamese outpatient population by selecting an appropriate population pharmacokinetic model of Tac for our patients.<br/><strong>Patients and Methods:</strong> The external dataset was obtained prospectively from 54 data of adult kidney transplant recipients treated at the 103 Military Hospital. All published Tac population pharmacokinetic models were systematically screened from PubMed and Scopus databases and were selected based on our patient’s available characteristics. Mean absolute prediction error (MAPE), mean prediction error, and goodness-of-fit plots were used to identify the appropriate model for finding the formula that identifies the influence of CYP3A5 genotype on the pharmacokinetic data of Vietnamese patients.<br/><strong>Results:</strong> The model of Zhu et al had a good predictive ability with MAPE of 19.29%. The influence of CYP3A5 genotype on tacrolimus clearance was expressed by the following formulas: <![CDATA[${rm{CL/F = 27,2 times }}left[{left({{rm{WT/70}}} right){rm{0,75}}} right]{rm{ times }}left[{left({{rm{HCT/0,35}}} right){rm{ - 0,501}}} right]rm{rm{ times }}left[{left({{rm{POD/180}}} right){rm{0,0306}}} right]{rm{ times CYP3A5 }}left({{rm{L/h}}} right)$]]>. The simulation result showed that Tac C₀ was significantly higher in patients not expressing CYP3A5 (p&lt; 0.001).<br/><strong>Conclusion:</strong> The incorporation of the CYP3A5 phenotype into Zhu’s structural model has significantly enhanced our ability to predict Tacrolimus trough levels in the Vietnamese population. This study’s results underscore the valuable role of CYP3A5 phenotype in optimizing the forecast of Tac concentrations, offering a promising avenue to assist health-care practitioners in their clinical decision-making and ultimately advance patient care outcomes.<br/><br/><strong>Keywords:</strong> tacrolimus, population pharmacokinetic, CYP3A5, Vietnam<br/>","PeriodicalId":501056,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":"242 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139662917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to: “Challenges in DPYD Test Implementation in Patients Treated with Fluoropyirimidines, is DPYD Genotype Arriving on Time?” [Response to Letter]","authors":"Cristina Montrasio, Stefania Cheli, Emilio Clementi","doi":"10.2147/pgpm.s456240","DOIUrl":"https://doi.org/10.2147/pgpm.s456240","url":null,"abstract":"Response to Letter in regards to Challenges in DPYD Test Implementation in Patients Treated with Fluoropyrimidines are DPYD Genotype Arriving on Time? [Letter]","PeriodicalId":501056,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139581637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of Opioid Receptor Gene Polymorphism on Fentanyl and Alfentanil’s Analgesic Effects in the Pediatric Perioperative Period","authors":"Jelena Lilic, Vesna G Marjanovic, Ivana Budic, Nikola Stefanovic, Dragana Stokanovic, Goran T Marjanovic, Tatjana Jevtovic-Stoimenov, Mladjan Golubovic, Maja Zecevic, Radmila Velickovic-Radovanovic","doi":"10.2147/pgpm.s443035","DOIUrl":"https://doi.org/10.2147/pgpm.s443035","url":null,"abstract":"<strong>Introduction:</strong> The polymorphism of the gene coding mu-opioid receptor (<em>OPRM1</em>) is one of the factors contributing to the variability in the response to opioid analgesics in children. The goal of this study is to investigate its role in association with postoperative acute pain in children of various ages.<br/><strong>Methods:</strong> This prospective study analyzed 110 pediatric patients, after plastic or orthopedic surgery, who were genotyped and randomly assigned to receive fentanyl or alfentanil. Postoperative pain was rated using Numerical Rating Scale (0– 10). All the patients were genotyped for<em>OPRM1 118A&gt;G</em> (<em>rs1799971</em>) gene polymorphism.<br/><strong>Results:</strong> School children under the age of 11 with the <em>OPRM1 AA</em> genotype were shown to have a higher BMI (p&lt; 0.05). Children over the age of 12 carrying G allele <em>OPRM1</em>, had increased postoperative pain sensitivity and intensity (3.28± 1.95 vs 4.91± 2.17; p&lt; 0.05), as compared to <em>AA</em> allele carriers.<br/><strong>Discussion:</strong> <em>OPRM1 118A&gt;G</em> polymorphism may explain the variation in the perception of postoperative pain in children over the age of 12 and may be a useful predictor for adjusting the dose of analgesics, but the dose is relative to the patient’s needs regardless of his genetic characteristics. In younger children, carriers of polymorphic <em>OPRM1 118G</em> allele may be protected from obesity, due to diminished <em>MOP</em> expression.<br/><br/><strong>Keywords:</strong> polymorphism, <em>OPRM1</em>, opioid, pain, children<br/>","PeriodicalId":501056,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":"138 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139581620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FBLN5 as One Presumably Prognostic Gene Potentially Modulating Tumor Immune Microenvironment for Renal Clear Cell Carcinoma in Children and Young Adults","authors":"Ming Zhang, Feng Chen, Shaoguang Feng, Xu Liu, Zhen Wang, Nan Shen, Lingjian Meng, Dongsheng Zhu, Zhitao Zhu","doi":"10.2147/pgpm.s442803","DOIUrl":"https://doi.org/10.2147/pgpm.s442803","url":null,"abstract":"<strong>Objective:</strong> To investigate the role of FBLN5in renal clear cell carcinoma (KIRC), in particular on the tumor’s immune microenvironment, including children and young adults.<br/><strong>Methods:</strong> FBLN5 expression in tumor and normal samples was explored using SangerBox, TIMER2.0, GEPIA, UALCAN, HPA databases. The Linkedomics database was used to obtain FBLN5 co-expressed genes in KIRC tissue. SangerBox was also used to estimate immune infiltration of FBLN5 in KIRC. The Kaplan-Meier plotter was used to investigate the survival effects of FBLN5 expression in the presence of immune infiltration. We then collected 48 cases from 7 hospitals over a-20 year period to calculate the impact of FBLN5 on the prognosis of children and young adults with KIRC.<br/><strong>Results:</strong> FBLN5 expression was significantly reduced in KIRC tissue compared to normal adjacent tissue. FBLN5 was potentially involved in the immune-related biological processes. In addition, FBLN5 expression has been linked to a number of immune checkpoints, cytokines, chemokines and chemokine receptors in KIRC. At the same time, the expression of FBLN5 affected the survival rates differently in KIRC patients with high or low levels of immune infiltration. High expression of FBLN5 in children and young adults with KIRC was associated with a favorable prognosis.<br/><strong>Conclusion:</strong> This study shed light on the potential of FBLN5 as a prognostic marker in children and young adults with KIRC and as an immune-related target for clinical treatment.<br/><br/><strong>Keywords:</strong> FBLN5, immune microenvironment, prognostic biomarker, kidney cancer, children<br/>","PeriodicalId":501056,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":"146 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139498499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternally Inherited Essential Hypertension May Be Associated with the Mutations in Mitochondrial tRNAGlu Gene","authors":"Chun Wang, Xin Deng, Lei Li, Mei Li","doi":"10.2147/pgpm.s436235","DOIUrl":"https://doi.org/10.2147/pgpm.s436235","url":null,"abstract":"<strong>Background:</strong> Mitochondrial DNA (mtDNA) mutations are associated with essential hypertension (EH), but the molecular mechanism remains largely unknown.<br/><strong>Objective:</strong> The aim of this study is to explore the association between mtDNA mutations and EH.<br/><strong>Methods:</strong> Two maternally inherited families with EH are underwent clinical, genetic and biochemical assessments. mtDNA mutations are screened by PCR-Sanger sequencing and phylogenetic, and bioinformatics analyses are performed to evaluate the pathogenicity of mtDNA mutations. We also generate cytoplasmic hybrid (cybrid) cell lines to analysis mitochondrial functions.<br/><strong>Results:</strong> Matrilineal relatives exhibit variable degree of clinical phenotypes. Molecular analysis reveals the presence of m.A14693G and m.A14696G mutations in two pedigrees. Notably, the m.A14693G mutation occurs at position 54 in the TψC loop of tRNA^Glu, a position which is critical for post-transcriptionally modification of tRNA^Glu. While the m.A14696G mutation creates a novel base-pairing (51C-64G). Bioinformatic analysis shows that these mutations alter tRNA^Glu secondary structure. Additionally, patients with tRNA^Glu mutations exhibit markedly decreased in mtDNA copy number, mitochondrial membrane potential (MMP) and ATP, whereas the levels of reactive oxygen species (ROS) increase significantly.<br/><strong>Conclusion:</strong> The m.A14696G and m.A14693G mutations lead to failure in tRNA^Glu metabolism and cause mitochondrial dysfunction that is responsible for EH.<br/><br/>","PeriodicalId":501056,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139398247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"circPVT1 Inhibits the Proliferation and Aids in Prediction of the Prognosis of Bladder Cancer","authors":"Hongyi Zhou, Xueping Cui, Leilei Zhu, Zhuoqun Xu, Zhuo Wang, Jianfeng Shao","doi":"10.2147/pgpm.s427147","DOIUrl":"https://doi.org/10.2147/pgpm.s427147","url":null,"abstract":"<strong>Background:</strong> Circular RNA PVT1 (circPVT1) is aberrantly expressed in several cancers, but its functional role and clinical relevance in bladder urothelial carcinoma (BLCA) remain unknown. This study aimed to identify the expression level of circPVT1 in BLCA and investigated its functional relevance with BLCA progression both in vitro and in vivo.<br/><strong>Methods:</strong> GEPIA, UALCAN, and OncoLnc were referred to presented data. Quantitative real-time PCR (qPCR) was used for the measurement of transnational expression of genes in BLCA specimens and cell lines. Immunohistochemistry (IHC) and fluorescence in situ hybridization analysis (FISH) assays were performed to detect HER2 amplification, Pearson’s correlation analysis to analyze the correlation between circPVT1 expression and clinical characteristics, Cox regression and K-M survival analyses to analyze prognostic factors. A nomogram was constructed for predicting prognosis. The proliferation of cells was measured by CCK-8 and colony formation assay, and the proliferation in vivo was evaluated using nude mouse models. qPCR was used to detect the expression of proliferation-related genes.<br/><strong>Results:</strong> circPVT1 was but mRNA PVT1 was not significantly overexpressed in BLCA. A high circPVT1 expression was associated with a better survival and negative HER2, but not with age, gender, and T stage. circPVT1 was an independent prognostic factor for the overall survival of BLCA patients. Knocking down circPVT1 promoted BLCA proliferation in vitro and in vivo. Knocking down circPVT1 upregulated ERBB2, MKI67, and PCNA expression and downregulated TP53 expression, but exerted no influence on CCND1 and CCNB1 expression.<br/><strong>Conclusion:</strong> circPVT1 is a tumor suppressor and novel prognostic biomarker for BLCA.<br/><br/>","PeriodicalId":501056,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":"48 3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139103819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Novel Prognostic Biomarkers That are Associated with Immune Microenvironment Based on GABA-Related Molecular Subtypes in Gastric Cancer [Corrigendum]","authors":"Beibei Wang, Linlin Huang, Shanliang Ye, Zhongwen Zheng, Shanying Liao","doi":"10.2147/pgpm.s452164","DOIUrl":"https://doi.org/10.2147/pgpm.s452164","url":null,"abstract":"Corrigendum for the article Identification of Novel Prognostic Biomarkers That are Associated with Immune Microenvironment Based on GABA-Related Molecular Subtypes in Gastric Cancer","PeriodicalId":501056,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139063012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenges in DPYD Test Implementation in Patients Treated with Fluoropyrimidines are DPYD Genotype Arriving on Time? [Letter]","authors":"Marta López López-Cepero, Antonia Obrador de Hevia, Mónica Guillot Morales","doi":"10.2147/pgpm.s450118","DOIUrl":"https://doi.org/10.2147/pgpm.s450118","url":null,"abstract":"<strong>","PeriodicalId":501056,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":"300 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139054309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heme Metabolism-Related Gene TENT5C is a Prognostic Marker and Investigating Its Immunological Role in Colon Cancer","authors":"Wei Han, Cheng Li, Yongheng Wang, Binliang Huo, Wenhan Li, Wen Shi","doi":"10.2147/pgpm.s433790","DOIUrl":"https://doi.org/10.2147/pgpm.s433790","url":null,"abstract":"<strong>Background:</strong> There is a strong correlation between consuming high amounts of heme and an elevated risk of developing various types of cancer, including colorectal cancer. However, the role of heme metabolism-related genes (HRGs) in colorectal cancer remains unclear. Our study aimed to identify prognostic markers for colorectal cancer patients based on these genes.<br/><strong>Methods:</strong> The heme metabolism score was assessed using gene set variation analysis (GSVA). Potential prognostic HRGs were identified from the TCGA-COAD dataset using LASSO and COX regression analyses. The expression level of TENT5C was validated in the GEO database and clinical samples. To explore the association between TENT5C expression and immune cell infiltrations, we performed ESTIMATE and single-sample gene set enrichment analysis (ssGSEA).<br/><strong>Results:</strong> The low level of heme metabolism score was associated with a poor prognosis in colorectal cancer patients. TENT5C is a prognostic gene and an independent prognostic biomarker for overall survival. Its expression was confirmed in multiple datasets and clinical samples, showing a positive correlation with immune cells and immune score. GSEA results suggested TENT5C’s significant role in regulating immune and inflammatory responses in colorectal cancer.<br/><strong>Conclusion:</strong> TENT5C can be used as a biomarker in colorectal cancer. Additionally, TENT5C is associated with both prognosis and immune infiltration. These findings lay a strong groundwork for future research to delve into the specific role of TENT5C in the development and advancement of colorectal cancer.<br/><br/>","PeriodicalId":501056,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":"171 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139023896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BICDL1 Predicts Poor Prognosis and is Correlated with Methylation and Immune Infiltration in Colorectal Cancer","authors":"Hongbiao Luo, Ji Luo, Ning Ding, Tao Zhang, Yongheng He","doi":"10.2147/pgpm.s424209","DOIUrl":"https://doi.org/10.2147/pgpm.s424209","url":null,"abstract":"<strong>Background:</strong> Bicaudal-D (BICD) Family Like Cargo Adaptor 1 (BICDL1) is an essential component of the molecular mechanism during neuronal development. However, BICDL1 has not been reported in cancer. Using bioinformatics analysis, we systematically evaluated the potential role of BICDL1 in CRC.<br/><strong>Methods:</strong> Colorectal cancer (CRC) and normal tissue samples were retrieved from the Gene Expression Omnibus (GEO), Genotype-Tissue Expression (GTEx), and Cancer Genome Atlas (TCGA) databases. Kaplan–Meier (K-M) analysis, nomogram, COX analysis, and receiver operating characteristic (ROC) curves were used to evaluate the prognostic power. Correlation analysis was also conducted to explore the correlation between mRNA expression and the methylation level of BICDL1 using cBioPortal, and the correlation between immune infiltration and BICDL1. RT-qPCR and Western blot assays were performed to analyze BICDL1 expression level between human colorectal cancer cell lines and normal colonic epithelial cells.<br/><strong>Results:</strong> BICDL1 had a higher expression in CRC tissues than in normal tissues (p &lt; 0.001) in TCGA and GES 74602 datasets. Kaplan-Meier survival analysis revealed that patients with high BICDL1 expression had lower overall survival (OS) (1.53, 95% confidence interval: 1.07– 2.17, p=0.019). The ROC curves demonstrated that BICDL1 has high specificity and efficiency in diagnosis (AUC=0.919, CI: 0.895– 0.943). The expression level of BICDL1 was significantly correlated with the infiltrating levels of Treg (R=0.146, p &lt; 0.001), TFH (R=0.080, p=0.043), NK CD56bright cells (R=0.149, p &lt; 0.001), aDC (R=0.095, p=0.016), and T helper cell infiltration (R=− 0.084, p=0.034). The correlation between BICDL1 expression and methylation levels was negative (R2=0.134, p &lt; 0.001), and CRC patients had lower methylation levels than normal people (p=0.036). BICDL1 mRNA and its protein expression levels in CRC cell lines (SW620) was markedly increased compared with that of normal colonic epithelial cells (NCM460) (p &lt; 0.001).<br/><strong>Conclusion:</strong> BICDL1 may be a potential biomarker for evaluating immune infiltration levels and prognosis of CRC.<br/><br/>","PeriodicalId":501056,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139025443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}