PharmacogenomicsPub Date : 2024-01-01Epub Date: 2024-12-19DOI: 10.1080/14622416.2024.2441104
Lisanne A H Bevers, Rebecca L Jensen, Andrew Owen, Angela Colbers, Daniel F Carr, David M Burger
{"title":"Genetic variation on dolutegravir pharmacokinetics and relation to safety and efficacy outcomes: a systematic review.","authors":"Lisanne A H Bevers, Rebecca L Jensen, Andrew Owen, Angela Colbers, Daniel F Carr, David M Burger","doi":"10.1080/14622416.2024.2441104","DOIUrl":"10.1080/14622416.2024.2441104","url":null,"abstract":"<p><strong>Background: </strong>Dolutegravir (DTG) is an antiviral agent used for the treatment of HIV, however, there is uncertainty over the influence of genetic variation on DTG exposure, and whether it has clinical implications for the efficacy or toxicity in different populations. This systematic review aims to create an overview of the impact of pharmacogenomics (PGx) on DTG exposure, efficacy, and toxicity.</p><p><strong>Methods: </strong>Publications up to 14 November 2023 were searched and articles were selected on the following criteria: original research articles providing data on people with HIV, data on PGx and either PK or PD or both PD and PGx.</p><p><strong>Results: </strong>711 records were identified, and after screening 10 articles were included. Commonly analyzed genes across the articles were <i>UGT1A1</i>, <i>ABCB1</i>, <i>ABCG2</i>, and <i>NR1I2</i>. The most reported variant associated with PD variability was in <i>SLC22A2</i>, with carriers at higher risk of neuropsychiatric adverse events.</p><p><strong>Conclusions: </strong>This review concludes that while PGx testing may help explain some variability in DTG pharmacokinetics when combined with therapeutic drug monitoring (TDM), current evidence is insufficient to support its routine clinical use. The role of PGx research for DTG remains relevant, especially in specific patient populations where interindividual PK variations are still unexplained.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"623-635"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"<i>MIR27A</i> rs895819 TC genotype increases risk of fluoropyrimidine-induced severe toxicity independently of <i>DPYD</i> variations.","authors":"Georgia Ragia, Eirini Biziota, Triantafyllia Koukaki, Kyriakos Amarantidis, Vangelis G Manolopoulos","doi":"10.2217/pgs-2023-0223","DOIUrl":"10.2217/pgs-2023-0223","url":null,"abstract":"<p><p><b>Aim:</b> MicroRNA 27a (miR-27a) regulates post-transcriptionally DPD activity. We have analyzed the association of <i>MIR27A</i> rs895819T>C variation, that modulates miR-27a expression, with fluropyrimidine-induced toxicity. <b>Materials & methods:</b> <i>MIR27A</i> rs895819T>C genotyping was conducted by TaqMan® allelic discrimination assay in 313 FP-treated cancer patients. <b>Results:</b> In overdominance (TC vs TT + CC), TC genotype was associated with grade 3-4 toxicity (p = 0.002), any grade toxicity (p = 0.052), and delayed drug administration or therapy discontinuation (p = 0.038). Odds of grade 3-4 toxicity were increased by both <i>DPYD</i> deficiency (OR: 8.923; p = 0.006) and <i>MIR27A</i> rs895819 TC genotype (OR: 3.865; p = 0.002). <b>Conclusion:</b> <i>MIR27A</i> rs895819 TC genotype is an independent risk factor for fluoropyrimidine-associated toxicity in the Greek population. Thus, <i>MIR27A</i> rs895819TC patients can be closely monitored for fluoropyrimidine-induced severe toxicity.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"59-67"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139730291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Screening and analysis of single nucleotide polymorphism in the 3'-UTR microRNA target regions and its implications for lung tumorigenesis.","authors":"Anmol Bhatia, Atul Kumar Upadhyay, Siddharth Sharma","doi":"10.1080/14622416.2024.2355864","DOIUrl":"10.1080/14622416.2024.2355864","url":null,"abstract":"<p><p><b>Aim:</b> The study aims to identify high-impact single nucleotide polymorphisms (SNPs) in miRNA target sites of genes associated with lung cancer.<b>Materials & methods:</b> Lung cancer genes were obtained from Uniprot KB. miRNA target site SNPs were mined from MirSNP, miRdSNP and TargetScan. SNPs were shortlisted based on binding impact, minor allele frequency and conservation. Gene expression was analyzed in genes with high-impact SNPs in healthy versus lung cancer tissue. Additionally, enrichment, pathway and network analyzes were performed.<b>Results:</b> 19 high-impact SNPs were identified in miRNA target sites of lung cancer-associated genes. These SNPs affect miRNA binding and gene expression. The genes are involved in key cancer related pathways.<b>Conclusion:</b> The identified high-impact miRNA target site SNPs and associated genes provide a starting point for case-control studies in lung cancer patients in different populations.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"299-314"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11404702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PharmacogenomicsPub Date : 2024-01-01Epub Date: 2024-07-29DOI: 10.1080/14622416.2024.2379227
Nikola Stefanović, Katarina Danković, Tatjana Cvetković, Stevan Vujić, Ivan Pavlović, Tatjana Jevtović-Stoimenov, Branka Mitić, Radmila Veličković-Radovanović
{"title":"Impact of IL-6 and IL-10 genotypes on tacrolimus dose requirements in kidney transplant recipients: Monte Carlo analysis.","authors":"Nikola Stefanović, Katarina Danković, Tatjana Cvetković, Stevan Vujić, Ivan Pavlović, Tatjana Jevtović-Stoimenov, Branka Mitić, Radmila Veličković-Radovanović","doi":"10.1080/14622416.2024.2379227","DOIUrl":"10.1080/14622416.2024.2379227","url":null,"abstract":"<p><p><b>Introduction:</b> IL-6 and IL-10 may affect the activity of cytochrome P450 (CYP) 3A enzymes involved in tacrolimus (Tac) metabolism. Moreover, the effect of IL-6 and IL-10 on Tac pharmacokinetics may differ with respect to the genetic variations in their genes.<b>Aim:</b> To examine the influence of IL-6 and IL-10 gene polymorphisms on Tac dose requirements and exposure over a 5-year period following kidney transplantation. Univariate and standard multivariate linear regression and Monte Carlo analysis were performed to investigate potential covariates influencing Tac dose-adjusted trough concentration (C<sub>0</sub>/D) in various post-transplantation periods.<b>Materials & methods:</b> IL-6 (-174G > C), IL-10 (-1082G > A, -819C > T and -592C > A) genotype, Tac daily dose, C<sub>0</sub>, C<sub>0</sub>/D and intrapatient variability data were collected from 113 patients.<b>Results:</b> Multivariate regression analysis and accompanied Monte Carlo simulation underscore the importance of considering IL-6 -174G > C and IL-10 -1082G > A gene polymorphisms, alongside Tac metabolic phenotype and post-transplantation period, when tailoring Tac dosage regimen.<b>Conclusion:</b> This study provides valuable insights regarding the individualized adjustment of Tac treatment in various post-transplantation periods.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"315-327"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11404698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PharmacogenomicsPub Date : 2024-01-01Epub Date: 2023-12-21DOI: 10.2217/pgs-2023-0199
Sara Abudahab, Patricia W Slattum, Elvin T Price, Joseph L McClay
{"title":"Epigenetic regulation of drug metabolism in aging: utilizing epigenetics to optimize geriatric pharmacotherapy.","authors":"Sara Abudahab, Patricia W Slattum, Elvin T Price, Joseph L McClay","doi":"10.2217/pgs-2023-0199","DOIUrl":"10.2217/pgs-2023-0199","url":null,"abstract":"<p><p>We explore the relationship between epigenetic aging and drug metabolism. We review current evidence for changes in drug metabolism in normal aging, followed by a description of how epigenetic modifications associated with age can regulate the expression and functionality of genes. In particular, we focus on the role of epigenome-wide studies of human and mouse liver in understanding these age-related processes with respect to xenobiotic processing. We highlight genes encoding drug metabolizing enzymes and transporters revealed to be affected by epigenetic aging in these studies. We conclude that substantial evidence exists for epigenetic aging impacting drug metabolism and transport genes, but more work is needed. We further highlight the promise of pharmacoepigenetics applied to enhancing drug safety in older adults.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"41-54"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10794944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138830881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PharmacogenomicsPub Date : 2024-01-01Epub Date: 2024-11-20DOI: 10.1080/14622416.2024.2429946
Esther Camilo Dos Reis, Santiago Caneppa, Pedro Vasconcelos, Paulo Caleb Júnior de Lima Santos
{"title":"Advancing pharmacogenomics research: automated extraction of insights from PubMed using SpaCy NLP framework.","authors":"Esther Camilo Dos Reis, Santiago Caneppa, Pedro Vasconcelos, Paulo Caleb Júnior de Lima Santos","doi":"10.1080/14622416.2024.2429946","DOIUrl":"10.1080/14622416.2024.2429946","url":null,"abstract":"<p><p>This paper presents a methodology for automatically extracting insights from PubMed articles using a Natural Language Processing (NLP) framework. Our approach, leveraging advanced NLP techniques and Named Entity Recognition (NER), is crucial for advancing pharmacogenomics and other scientific fields that benefit from streamlined access to literature through automated services like RESTful APIs.Building a new NLP model presents several challenges. First, it is essential to have a thorough understanding of the field in order to define relevant entities. Second, the construction of a diverse and consistent set of examples is crucial. Finally, the effective utilization of pre-established models is of paramount importance, as demonstrated in this work.Our model, validated via ten-fold cross-validation, achieved over 70% recall and precision for all entities in the training set. We provide a reproducible pipeline for the scientific community and propose a structured approach for qualitative analysis and clustering of results. This methodology refines literature reviews, optimizes knowledge extraction, and supports broader application across diverse research domains. An online platform could further extend these benefits to researchers, educators, and practitioners.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"573-578"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PharmacogenomicsPub Date : 2024-01-01Epub Date: 2024-09-04DOI: 10.1080/14622416.2024.2392479
Eve Tomlinson, Chris Cooper, Hayley E Jones, Catalina Lopez Manzano, Rachel Palmer, Joe Carroll, Ayman Sadek, Nicky J Welton, Mariska Leeflang, Penny Whiting
{"title":"Accuracy and technical characteristics of CYP2C19 point of care tests: a systematic review.","authors":"Eve Tomlinson, Chris Cooper, Hayley E Jones, Catalina Lopez Manzano, Rachel Palmer, Joe Carroll, Ayman Sadek, Nicky J Welton, Mariska Leeflang, Penny Whiting","doi":"10.1080/14622416.2024.2392479","DOIUrl":"10.1080/14622416.2024.2392479","url":null,"abstract":"<p><p><b>Aim:</b> To assess the accuracy and technical characteristics of <i>CYP2C19</i> point of care tests (POCTs).<b>Patients & methods:</b> Systematic review of primary studies, in any population or setting, that evaluated POCTs for detecting <i>CYP2C19</i> loss of function (LOF) alleles.<b>Results:</b> Eleven studies provided accuracy data (eight Spartan; one Genomadix Cube; one GMEX; one Genedrive). The POCTs had very high sensitivity and specificity for the alleles they tested for. Twenty-two studies reported technical characteristics: POCTs were easy to operate and provided results quickly. Limited data were reported for test failure rate and cost.<b>Conclusion:</b> <i>CYP2C19</i> POCTs may be a useful alternative to laboratory-based testing to guide antiplatelet therapy. Further data are required on accuracy (GMEX; Genedrive), test failure and cost (all POCT).</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"407-423"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PharmacogenomicsPub Date : 2024-01-01Epub Date: 2024-07-29DOI: 10.1080/14622416.2024.2375190
Dewa A S Handani, Adam Hermawan, Zullies Ikawati
{"title":"Correlation of <i>ACE</i> insertion/deletion gene polymorphism with captopril effectiveness in Indonesian hypertensive patients.","authors":"Dewa A S Handani, Adam Hermawan, Zullies Ikawati","doi":"10.1080/14622416.2024.2375190","DOIUrl":"10.1080/14622416.2024.2375190","url":null,"abstract":"<p><p><b>Background:</b> Hypertension is a prevalent health concern in Indonesia, with a high percentage of patients unresponsive to ACE inhibitor treatment. <b>Methods:</b> This multicenter case-control study investigated the correlation between ACE I/D and captopril effectiveness in Indonesian hypertensive patients. Hypertensive patients were divided into control (n = 69) and case (n = 73) groups. <i>ACE I/D</i> was identified using PCR and electrophoresis.<b>Results:</b> No significant differences in genotype frequencies or allele distribution were observed. The difference of blood pressure reduction among the three genotypes also lacked statistical significance.<b>Conclusion: </b> <i>ACE I/D</i> is not significantly associated with blood pressure reduction following captopril therapy in Indonesian hypertensive patients. These results underscore the limited predictive utility of <i>ACE I/D</i> in managing hypertension with captopril.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"357-365"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11734884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PharmacogenomicsPub Date : 2024-01-01Epub Date: 2023-12-22DOI: 10.2217/pgs-2023-0148
Fang Cheng, Chao-Chao Qiu, Xian-Gao Jiang, Te Wu, Qiang Zhang, Xin Chen, Shi-Lin Zheng, Sai-Duo Liu, Xin-Chun Ye, Ji-Chan Shi
{"title":"Relevance of <i>NAT2</i> genotype and clinical factors to risk for antituberculosis drug-induced liver injury.","authors":"Fang Cheng, Chao-Chao Qiu, Xian-Gao Jiang, Te Wu, Qiang Zhang, Xin Chen, Shi-Lin Zheng, Sai-Duo Liu, Xin-Chun Ye, Ji-Chan Shi","doi":"10.2217/pgs-2023-0148","DOIUrl":"10.2217/pgs-2023-0148","url":null,"abstract":"<p><p>The study analyzes the risk factors associated with antituberculosis drug-induced liver injury (ATB-DILI), and the relationship between ATB-DILI and <i>NAT2</i> gene polymorphisms. Out of the 324 included patients, 57 (17.59%) developed ATB-DILI. Age, history of liver disease, alcohol consumption and timing of antituberculosis (ATB) treatment were independent risk factors for ATB-DILI in the patients with tuberculosis (TB; p < 0.05). There was a significant difference in the distribution of <i>NAT2</i> metabolic phenotypes between the study group and the control group (p < 0.05). The ATB drug treatment for pulmonary TB can cause a high incidence of ATB-DILI. Age, history of liver disease, alcohol consumption and timing of ATB treatment are independent risk factors for ATB-DILI in patients with TB.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"21-28"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138830882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PharmacogenomicsPub Date : 2024-01-01Epub Date: 2024-02-02DOI: 10.2217/pgs-2023-0173
Xueting Zhu, Guanghua Luo, Lu Zheng
{"title":"Update on <i>HLA-B*15:02</i> allele associated with adverse drug reactions.","authors":"Xueting Zhu, Guanghua Luo, Lu Zheng","doi":"10.2217/pgs-2023-0173","DOIUrl":"10.2217/pgs-2023-0173","url":null,"abstract":"<p><p>HLA alleles, part of the major histocompatibility complex, are strongly associated with adverse drug reactions (ADRs). This review focuses on <i>HLA-B*15:02</i> and explores its association with ADRs in various ethnic populations and with different drugs, aiming to provide insights into the safe clinical use of drugs and minimize the occurrence of ADRs. Furthermore, the review explores the potential mechanisms by which <i>HLA-B*15:02</i> may be associated with ADRs, aiming to gain new insights into drug modification and identification of haptens. In addition, it analyzes the frequency of the <i>HLA-B*15:02</i>, genotyping methods, cost-effectiveness and treatment measures for adverse reactions, thereby providing a theoretical basis for formulating clinical treatment plans.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"97-111"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139672403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}