PharmacogenomicsPub Date : 2024-03-01Epub Date: 2024-03-21DOI: 10.2217/pgs-2024-0026
Bani Jolly, Vinod Scaria
{"title":"Ethnic differences in pharmacogenomic variants: a south Asian perspective.","authors":"Bani Jolly, Vinod Scaria","doi":"10.2217/pgs-2024-0026","DOIUrl":"10.2217/pgs-2024-0026","url":null,"abstract":"","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"171-174"},"PeriodicalIF":2.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140175955","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 : 2024-02-01Epub Date: 2024-03-05DOI: 10.2217/pgs-2023-0193
Rebekah Ryanne Wu, Richelle Benevent, Nina R Sperber, Jill S Bates, Daniel Villa, Dilhan Weeraratne, Timothy A Burrell, Deepak Voora
{"title":"Workforce readiness for pharmacogenomics and key elements for sustainment within the Veterans Health Administration.","authors":"Rebekah Ryanne Wu, Richelle Benevent, Nina R Sperber, Jill S Bates, Daniel Villa, Dilhan Weeraratne, Timothy A Burrell, Deepak Voora","doi":"10.2217/pgs-2023-0193","DOIUrl":"10.2217/pgs-2023-0193","url":null,"abstract":"<p><p><b>Aim:</b> Understanding barriers and facilitators to pharmacogenomics (PGx) implementation and how to structure a clinical program with the Veterans Health Administration (VA). <b>Materials & methods:</b> Healthcare provider (HCP) survey at 20 VA facilities assessing PGx knowledge/acceptance and qualitative interviews to understand how best to design and sustain a national program. <b>Results:</b> 186 (12% response rate) surveyed believed PGx informs drug efficacy (74.7%) and adverse events (71.0%). Low confidence in knowledge (43.0%) and ability to implement (35.4-43.5%). 23 (60.5% response rate) interviewees supported a nationally program to oversee VA education, consultation and IT resources. Prescribing HCPs should be directing local activities. <b>Conclusion:</b> HCPs recognize PGx value but are not prepared to implement. Healthcare systems should build system-wide programs for implementation education and support.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"133-145"},"PeriodicalIF":1.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10964838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140028675","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 : 2024-02-01Epub Date: 2024-03-20DOI: 10.2217/pgs-2023-0229
Ana I Lopez-Medina, Alessandra M Campos-Staffico, Choudhary Anwar A Chahal, Isabella Volkers, Juliet P Jacoby, Omer Berenfeld, Jasmine A Luzum
{"title":"Genetic risk factors for drug-induced long QT syndrome: findings from a large real-world case-control study.","authors":"Ana I Lopez-Medina, Alessandra M Campos-Staffico, Choudhary Anwar A Chahal, Isabella Volkers, Juliet P Jacoby, Omer Berenfeld, Jasmine A Luzum","doi":"10.2217/pgs-2023-0229","DOIUrl":"10.2217/pgs-2023-0229","url":null,"abstract":"<p><p><b>Aim:</b> Drug-induced long QT syndrome (diLQTS), an adverse effect of many drugs, can lead to sudden cardiac death. Candidate genetic variants in cardiac ion channels have been associated with diLQTS, but several limitations of previous studies hamper clinical utility. <b>Materials & methods:</b> Thus, the purpose of this study was to assess the associations of <i>KCNE1</i>-D85N, <i>KCNE2</i>-I57T and <i>SCN5A</i>-G615E with diLQTS in a large observational case-control study (6,083 self-reported white patients treated with 27 different high-risk QT-prolonging medications; 12.0% with diLQTS). <b>Results:</b> <i>KCNE1</i>-D85N significantly associated with diLQTS (adjusted odds ratio: 2.24 [95% CI: 1.35-3.58]; p = 0.001). Given low minor allele frequencies, the study had insufficient power to analyze <i>KCNE2</i>-I57T and <i>SCN5A</i>-G615E. <b>Conclusion:</b> <i>KCNE1</i>-D85N is a risk factor for diLQTS that should be considered in future clinical practice guidelines.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":"25 3","pages":"117-131"},"PeriodicalIF":1.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10964839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140175960","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}
{"title":"The genomic landscape of <i>CYP2D6</i> variation in the Indian population.","authors":"Ambily Sivadas, Surabhi Rathore, S Sahana, Bani Jolly, Rahul C Bhoyar, Abhinav Jain, Disha Sharma, Mohamed Imran, Vigneshwar Senthilvel, Mohit Kumar Divakar, Anushree Mishra, Sridhar Sivasubbu, Vinod Scaria","doi":"10.2217/pgs-2023-0233","DOIUrl":"10.2217/pgs-2023-0233","url":null,"abstract":"<p><p><b>Aim:</b> The <i>CYP2D6</i> gene is highly polymorphic, causing large interindividual variability in the metabolism of several clinically important drugs. <b>Materials & methods:</b> The authors investigated the diversity and distribution of <i>CYP2D6</i> alleles in Indians using whole genome sequences (N = 1518). Functional consequences were assessed using pathogenicity scores and molecular dynamics simulations. <b>Results:</b> The analysis revealed population-specific <i>CYP2D6</i> alleles (<i>*86</i>, <i>*7</i>, <i>*111</i>, <i>*112</i>, <i>*113</i>, <i>*99</i>) and remarkable differences in variant and phenotype frequencies with global populations. The authors observed that one in three Indians could benefit from a dose alteration for psychiatric drugs with accurate <i>CYP2D6</i> phenotyping. Molecular dynamics simulations revealed large conformational fluctuations, confirming the predicted reduced function of <i>*86</i> and <i>*113</i> alleles. <b>Conclusion:</b> The findings emphasize the utility of comprehensive <i>CYP2D6</i> profiling for aiding precision public health.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"147-160"},"PeriodicalIF":2.1,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139997083","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 : 2024-02-01Epub Date: 2024-03-05DOI: 10.2217/pgs-2023-0238
Francesco Pepe, Konstantinos Venetis, Giulia Cursano, Chiara Frascarelli, Pasquale Pisapia, Davide Vacirca, Claudia Scimone, Alessandra Rappa, Gianluca Russo, Eltjona Mane, Fabio Pagni, Isabella Castellano, Giancarlo Troncone, Carmine De Angelis, Giuseppe Curigliano, Elena Guerini-Rocco, Umberto Malapelle, Nicola Fusco
{"title":"<i>PIK3CA</i> testing in hormone receptor-positive/HER2-negative metastatic breast cancer: real-world data from Italian molecular pathology laboratories.","authors":"Francesco Pepe, Konstantinos Venetis, Giulia Cursano, Chiara Frascarelli, Pasquale Pisapia, Davide Vacirca, Claudia Scimone, Alessandra Rappa, Gianluca Russo, Eltjona Mane, Fabio Pagni, Isabella Castellano, Giancarlo Troncone, Carmine De Angelis, Giuseppe Curigliano, Elena Guerini-Rocco, Umberto Malapelle, Nicola Fusco","doi":"10.2217/pgs-2023-0238","DOIUrl":"10.2217/pgs-2023-0238","url":null,"abstract":"<p><p><b>Introduction:</b> <i>PIK3CA</i> gene mutations occur in approximately 40% of hormone receptor-positive/HER2-negative (HR<sup>+</sup>/HER2<sup>-</sup>) metastatic breast cancers (MBCs), electing them to targeted therapy. Testing <i>PIK3CA</i> status is complex due to selection of biological specimen and testing method. <b>Materials & methods:</b> This work investigates real-life experience on <i>PIK3CA</i> testing in HR<sup>+</sup>/HER2<sup>-</sup> MBC. Clinical, technical and molecular data on <i>PIK3CA</i> testing were collected from two referral laboratories. Additionally, the results of a nationwide <i>PIK3CA</i> survey involving 116 institutions were assessed. <b>Results:</b> Overall, n = 35 MBCs were <i>PIK3CA</i>-mutated, with mutations mostly occurring in exons 9 (n = 19; 51.4%) and 20 (n = 15; 40.5%). The nationwide survey revealed significant variability across laboratories in terms of sampling methodology, technical assessment and clinical report signing healthcare figures for <i>PIK3CA</i> molecular testing in diagnostic routine practice. <b>Conclusion:</b> This study provides insights into the real-world routine of <i>PIK3CA</i> testing in HR<sup>+</sup>/HER2<sup>-</sup> MBC and highlights the need for standardization and networking in predictive pathology.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"161-169"},"PeriodicalIF":2.1,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140028674","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: 2023-12-19DOI: 10.2217/pgs-2023-0228
Sarah Jones
{"title":"Overview of the year 2023 at <i>Pharmacogenomics</i>.","authors":"Sarah Jones","doi":"10.2217/pgs-2023-0228","DOIUrl":"10.2217/pgs-2023-0228","url":null,"abstract":"","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"1-3"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138807394","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: 2024-10-25DOI: 10.1080/14622416.2024.2409060
Alenka Šmid, Dunja Urbančič, Jaka Vrevc Žlajpah, Natalia Stollarova, Tomaž Prelog, Marko Kavčič, Janez Jazbec, Irena Mlinarič-Raščan, Nataša Karas Kuželički
{"title":"Genetic profiling of <i>NUDT15</i> in the Slovenian population.","authors":"Alenka Šmid, Dunja Urbančič, Jaka Vrevc Žlajpah, Natalia Stollarova, Tomaž Prelog, Marko Kavčič, Janez Jazbec, Irena Mlinarič-Raščan, Nataša Karas Kuželički","doi":"10.1080/14622416.2024.2409060","DOIUrl":"10.1080/14622416.2024.2409060","url":null,"abstract":"<p><p>Determining variant <i>TPMT</i> alleles to predict patient response to thiopurine therapy represents one of the first successful implementations of pharmacogenomics in clinical practice. However, despite the <i>TPMT</i>-adjusted thiopurine dosing, some <i>TPMT</i> wild-type patients still exhibit toxicity at standard doses. Over the past decade, the pharmacogene <i>NUDT15</i> has emerged as a significant co-modulator of thiopurine therapy. Initially, <i>NUDT15</i> was considered important predominantly in Asian populations, but recent studies have highlighted its relevance in European populations as well.To evaluate the pharmacogenetic significance of <i>NUDT15</i> in the Slovenian population, we sequenced extended regions of exon 1 and exon 3 in 109 healthy individuals and 37 patients with acute lymphoblastic leukemia.We identified eight variants, including one with established clinical significance (allele *3) and one extremely rare variant (Chr13 at 48045861; GRCh38, NC_000013.11). The frequencies of most previously described variants in both the general population and in the ALL cohort were consistent with those reported in other European populations, except for rs45465203, which was less frequent in the Slovenian population. None of the variants, except for <i>NUDT15*3</i>, were associated with cumulative thiopurine doses in ALL patients. However, these variants warrant further investigation in larger ALL cohorts.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"515-525"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505804","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: 2024-11-15DOI: 10.1080/14622416.2024.2428587
Susanne B Haga
{"title":"Artificial intelligence, medications, pharmacogenomics, and ethics.","authors":"Susanne B Haga","doi":"10.1080/14622416.2024.2428587","DOIUrl":"10.1080/14622416.2024.2428587","url":null,"abstract":"<p><p>Artificial Intelligence (AI) and Machine Learning (ML) are revolutionizing various scientific and clinical disciplines including pharmacogenomics (PGx) by enabling the analysis of complex datasets and the development of predictive models. The integration of AI and ML with PGx has the potential to provide more precise, data-driven insights into new drug targets, drug efficacy, drug selection, and risk of adverse events. While significant effort to develop and validate these tools remain, ongoing advancements in AI technologies, coupled with improvements in data quality and depth is anticipated to drive the transition of these tools into clinical practice and delivery of individualized treatments and improved patient outcomes. The successful development and integration of AI-assisted PGx tools will require careful consideration of ethical, legal, and social issues (ELSI) in research and clinical practice. This paper explores the intersection of PGx with AI, highlighting current research and potential clinical applications, and ELSI including privacy, oversight, patient and provider knowledge and acceptance, and the impact on patient-provider relationship and new roles.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"611-622"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639446","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: 2025-01-14DOI: 10.1080/14622416.2025.2452835
Priyanga Ranasinghe, Pulasthi B Gunarathna, Hajanthy Jeyapragasam, Nirmala Sirisena, D P Bhagya Hendalage, Vajira H W Dissanayake
{"title":"<i>CYP2C19</i> and <i>CES1</i> gene variants affecting clopidogrel metabolism in a South Asian population from Sri Lanka.","authors":"Priyanga Ranasinghe, Pulasthi B Gunarathna, Hajanthy Jeyapragasam, Nirmala Sirisena, D P Bhagya Hendalage, Vajira H W Dissanayake","doi":"10.1080/14622416.2025.2452835","DOIUrl":"10.1080/14622416.2025.2452835","url":null,"abstract":"<p><strong>Aims: </strong>Clopidogrel exhibits substantial variability in therapeutic response, largely contributed by genetic factors. The pharmacogenomic variants data on clopidogrel metabolism in South Asians have been sparsely studied. This study explores the impact of <i>CYP2C19</i> and <i>CES1</i> gene variants on clopidogrel metabolism in Sri Lankans, revealing significant pharmacogenomic insights with broader implications for South Asians.</p><p><strong>Materials & methods: </strong>Genotype data were filtered out from an anonymized database of 690 Sri Lankans, and minor allele frequencies (MAFs) were calculated. Five variants of <i>CYP2C19</i> and one variant of <i>CES1</i> gene were studied.</p><p><strong>Results: </strong>Among the five <i>CYP2C19</i> variants studied, rs12769205 (A>G) and rs4244285 (G>A) had the highest MAF of 42.1% and 42.0%, respectively. The <i>CES1</i> variant rs71647871 (C>T) showed a MAF of 0.2%. Sri Lankans exhibited significantly higher MAFs for key variants compared to populations such as Europeans, African Americans, and East Asians (<i>p</i> < 0.05).</p><p><strong>Conclusion: </strong>Given that South Asians share genetic similarities, these findings suggest that a substantial proportion of the region's population may also be poor responders to clopidogrel, increasing the risk of adverse outcomes. This highlights the importance of genotype-guided antiplatelet therapy, which could improve clinical outcomes across South Asia amidst rising cardiovascular disease rates.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"657-660"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984386","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}