Pharmacogenomics最新文献_第4页

Genetic risk factors for drug-induced long QT syndrome: findings from a large real-world case-control study. 药物诱发长 QT 综合征的遗传风险因素：一项大型真实病例对照研究的发现。

IF 1.9 4区医学

Pharmacogenomics Pub Date : 2024-02-01 Epub Date: 2024-03-20 DOI: 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":"Aim: 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. Materials & methods: Thus, the purpose of this study was to assess the associations of KCNE1-D85N, KCNE2-I57T and SCN5A-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). Results: KCNE1-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 KCNE2-I57T and SCN5A-G615E. Conclusion: KCNE1-D85N is a risk factor for diLQTS that should be considered in future clinical practice guidelines.","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}

引用次数: 0

The genomic landscape of CYP2D6 variation in the Indian population. 印度人群中 CYP2D6 变异的基因组图谱。

IF 2.1 4区医学

Pharmacogenomics Pub Date : 2024-02-01 Epub Date: 2024-03-01 DOI: 10.2217/pgs-2023-0233

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

{"title":"The genomic landscape of CYP2D6 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":"Aim: The CYP2D6 gene is highly polymorphic, causing large interindividual variability in the metabolism of several clinically important drugs. Materials & methods: The authors investigated the diversity and distribution of CYP2D6 alleles in Indians using whole genome sequences (N = 1518). Functional consequences were assessed using pathogenicity scores and molecular dynamics simulations. Results: The analysis revealed population-specific CYP2D6 alleles (*86, *7, *111, *112, *113, *99) 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 CYP2D6 phenotyping. Molecular dynamics simulations revealed large conformational fluctuations, confirming the predicted reduced function of *86 and *113 alleles. Conclusion: The findings emphasize the utility of comprehensive CYP2D6 profiling for aiding precision public health.","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}

引用次数: 0

PIK3CA testing in hormone receptor-positive/HER2-negative metastatic breast cancer: real-world data from Italian molecular pathology laboratories. 激素受体阳性/HER2 阴性转移性乳腺癌的 PIK3CA 检测：来自意大利分子病理实验室的真实数据。

IF 2.1 4区医学

Pharmacogenomics Pub Date : 2024-02-01 Epub Date: 2024-03-05 DOI: 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":"PIK3CA 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":"Introduction: PIK3CA gene mutations occur in approximately 40% of hormone receptor-positive/HER2-negative (HR+/HER2-) metastatic breast cancers (MBCs), electing them to targeted therapy. Testing PIK3CA status is complex due to selection of biological specimen and testing method. Materials & methods: This work investigates real-life experience on PIK3CA testing in HR+/HER2- MBC. Clinical, technical and molecular data on PIK3CA testing were collected from two referral laboratories. Additionally, the results of a nationwide PIK3CA survey involving 116 institutions were assessed. Results: Overall, n = 35 MBCs were PIK3CA-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 PIK3CA molecular testing in diagnostic routine practice. Conclusion: This study provides insights into the real-world routine of PIK3CA testing in HR+/HER2- MBC and highlights the need for standardization and networking in predictive pathology.","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}

引用次数: 0

Overview of the year 2023 at Pharmacogenomics. 药物基因组学 2023 年概览。

IF 2.1 4区医学

Pharmacogenomics Pub Date : 2024-01-01 Epub Date: 2023-12-19 DOI: 10.2217/pgs-2023-0228

Sarah Jones

引用次数: 0

Genetic profiling of NUDT15 in the Slovenian population. 斯洛文尼亚人群中 NUDT15 的基因图谱分析。

IF 1.9 4区医学

Pharmacogenomics Pub Date : 2024-01-01 Epub Date: 2024-10-25 DOI: 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 NUDT15 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":"Determining variant TPMT alleles to predict patient response to thiopurine therapy represents one of the first successful implementations of pharmacogenomics in clinical practice. However, despite the TPMT-adjusted thiopurine dosing, some TPMT wild-type patients still exhibit toxicity at standard doses. Over the past decade, the pharmacogene NUDT15 has emerged as a significant co-modulator of thiopurine therapy. Initially, NUDT15 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 NUDT15 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 NUDT15*3, were associated with cumulative thiopurine doses in ALL patients. However, these variants warrant further investigation in larger ALL cohorts.","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}

引用次数: 0

Artificial intelligence, medications, pharmacogenomics, and ethics. 人工智能、药物、药物基因组学和伦理。

IF 1.9 4区医学

Pharmacogenomics Pub Date : 2024-01-01 Epub Date: 2024-11-15 DOI: 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":"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.","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"611-622"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11703462/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CYP2C19 and CES1 gene variants affecting clopidogrel metabolism in a South Asian population from Sri Lanka. 斯里兰卡南亚人群中影响氯吡格雷代谢的 CYP2C19 和 CES1 基因变异。

IF 1.9 4区医学

Pharmacogenomics Pub Date : 2024-01-01 Epub Date: 2025-01-14 DOI: 10.1080/14622416.2025.2452835

Priyanga Ranasinghe, Pulasthi B Gunarathna, Hajanthy Jeyapragasam, Nirmala Sirisena, D P Bhagya Hendalage, Vajira H W Dissanayake

{"title":"CYP2C19 and CES1 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":"Aims: 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 CYP2C19 and CES1 gene variants on clopidogrel metabolism in Sri Lankans, revealing significant pharmacogenomic insights with broader implications for South Asians.Materials & methods: Genotype data were filtered out from an anonymized database of 690 Sri Lankans, and minor allele frequencies (MAFs) were calculated. Five variants of CYP2C19 and one variant of CES1 gene were studied.Results: Among the five CYP2C19 variants studied, rs12769205 (A>G) and rs4244285 (G>A) had the highest MAF of 42.1% and 42.0%, respectively. The CES1 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 (p < 0.05).Conclusion: 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.","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}

引用次数: 0

Pharmacogenetics of Calcineurin inhibitors in kidney transplant recipients: the African gap. A narrative review. 肾移植受者钙神经蛋白抑制剂的药物遗传学：非洲差距。叙述性综述。

IF 1.9 4区医学

Pharmacogenomics Pub Date : 2024-01-01 Epub Date: 2024-08-07 DOI: 10.1080/14622416.2024.2370761

Sadiq Aliyu Hussaini, Bala Waziri, Caroline Dickens, Raquel Duarte

{"title":"Pharmacogenetics of Calcineurin inhibitors in kidney transplant recipients: the African gap. A narrative review.","authors":"Sadiq Aliyu Hussaini, Bala Waziri, Caroline Dickens, Raquel Duarte","doi":"10.1080/14622416.2024.2370761","DOIUrl":"10.1080/14622416.2024.2370761","url":null,"abstract":"Calcineurin inhibitors (CNIs) are the mainstay of immunosuppression in kidney transplantation. Interpatient variability in the disposition of calcineurin inhibitors is a well-researched phenomenon and has a well-established genetic contribution. There is great diversity in the makeup of African genomes, but very little is known about the pharmacogenetics of CNIs and transplant outcomes. This review focuses on genetic variants of calcineurin inhibitors' metabolizing enzymes (CYP3A4, CYP3A5), related molecules (POR, PPARA) and membrane transporters involved in the metabolism of calcineurin inhibitors. Given the genetic diversity across the African continent, it is imperative to generate pharmacogenetic data, especially in the era of personalized medicine and emphasizes the need for studies specific to African populations. The study of allelic variants in populations where they have greater frequencies will help answer questions regarding their impact. We aim to fill the knowledge gaps by reviewing existing research and highlighting areas where African research can contribute.","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"329-341"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11404701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141898013","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}

引用次数: 0

Predicting laboratory aspirin resistance in Chinese stroke patients using machine learning models by GP1BA polymorphism. 利用GP1BA多态性的机器学习模型预测中国脑卒中患者的实验室阿司匹林耐药性

IF 1.9 4区医学

Pharmacogenomics Pub Date : 2024-01-01 Epub Date: 2024-10-23 DOI: 10.1080/14622416.2024.2411939

Jun Liu, Linkun Pan, Sheng Wang, Yueran Li, Yilai Wu, Jiajie Luan, Kui Yang

引用次数: 0

Pharmacogenetic and pharmacogenomic treatment of rheumatoid arthritis: a review of Pharmacogenomics Knowledge Base scientific evidence. 类风湿性关节炎的药物遗传学和药物基因组学治疗：药物基因组学知识库科学证据综述。

IF 2.1 4区医学

Pharmacogenomics Pub Date : 2024-01-01 Epub Date: 2024-01-17 DOI: 10.2217/pgs-2023-0230

Pedro Dorado, Eva M Peñas-Lledó

引用次数: 0