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Pharmacogenomic implications of the differential distribution of CYP3A5 metabolic phenotypes among Latin American populations. 拉丁美洲人群中 CYP3A5 代谢表型不同分布的药物基因组学意义。
IF 2.1 4区 医学
Pharmacogenomics Pub Date : 2024-03-01 Epub Date: 2024-03-20 DOI: 10.2217/pgs-2024-0009
Guilherme Suarez-Kurtz, Claudio José Struchiner
{"title":"Pharmacogenomic implications of the differential distribution of CYP3A5 metabolic phenotypes among Latin American populations.","authors":"Guilherme Suarez-Kurtz, Claudio José Struchiner","doi":"10.2217/pgs-2024-0009","DOIUrl":"10.2217/pgs-2024-0009","url":null,"abstract":"<p><p>This study shows that the distribution of <i>CYP3A5</i> alleles (<i>*1</i>, <i>*3</i>, <i>*6</i> and <i>*7</i>) and genotype-predicted CYP3A5 phenotypes vary significantly across Latin American cohorts (Brazilians and the One Thousand Genomes Admixed American superpopulation), as well as among subcohorts comprising individuals with the highest proportions of Native, European or sub-Saharan African ancestry. Differences in biogeographical ancestry across the study groups are the likely explanation for these results. The differential distribution of CYP3A5 phenotypes has major pharmacogenomic implications, affecting the proportion of individuals carrying high risk CYP3A5 phenotypes for the immunosuppressant tacrolimus and the number of patients that would need to be genotyped to prevent acute rejection in kidney transplant recipients under tacrolimus treatment.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140175958","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
Knowledge and perceptions of pharmacogenomics among pharmacists in Manitoba, Canada. 加拿大马尼托巴省药剂师对药物基因组学的了解和看法。
IF 2.1 4区 医学
Pharmacogenomics Pub Date : 2024-03-01 Epub Date: 2024-03-20 DOI: 10.2217/pgs-2024-0013
Abdullah Al Maruf, Meagan Shields, Amber Fryza, Amanda Wondrasek, Christine Leong, Kaarina Kowalec, Chad Bousman
{"title":"Knowledge and perceptions of pharmacogenomics among pharmacists in Manitoba, Canada.","authors":"Abdullah Al Maruf, Meagan Shields, Amber Fryza, Amanda Wondrasek, Christine Leong, Kaarina Kowalec, Chad Bousman","doi":"10.2217/pgs-2024-0013","DOIUrl":"10.2217/pgs-2024-0013","url":null,"abstract":"<p><p><b>Objective:</b> This work was designed to describe the knowledge and perceptions of pharmacogenomics (PGx) among pharmacists in the Canadian province of Manitoba. <b>Methods:</b> A 40-item, web-based survey was distributed to pharmacists in Manitoba. <b>Results:</b> Of 74 participants, one third had some education or training in PGx, and 12.2% had used PGx test results in their practice. Participants' self-rated knowledge of PGx testing and common PGx resources (e.g., Pharmacogenomics Knowledge Base, Clinical Pharmacogenetics Implementation Consortium) was low. Most pharmacists surveyed believe that PGx can improve medication efficacy (82.4%) or prevent adverse drug reactions (81.1%). Most (91%) desired more education on PGx. <b>Conclusion:</b> Manitoba pharmacists reported positive perceptions toward PGx. However, they are currently underprepared to implement PGx into practice.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140175957","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
Implementation of whole-exome sequencing for pharmacogenomics profiling and exploring its potential clinical utilities. 采用全外显子组测序进行药物基因组学分析，探索其潜在的临床用途。
IF 2.1 4区 医学
Pharmacogenomics Pub Date : 2024-03-01 Epub Date: 2024-03-21 DOI: 10.2217/pgs-2023-0243
Danyi Wang, Jayaprakasam Bolleddula, Anna Coenen-Stass, Thomas Grombacher, Jennifer Q Dong, Juergen Scheuenpflug, Giuseppe Locatelli, Zheng Feng
{"title":"Implementation of whole-exome sequencing for pharmacogenomics profiling and exploring its potential clinical utilities.","authors":"Danyi Wang, Jayaprakasam Bolleddula, Anna Coenen-Stass, Thomas Grombacher, Jennifer Q Dong, Juergen Scheuenpflug, Giuseppe Locatelli, Zheng Feng","doi":"10.2217/pgs-2023-0243","DOIUrl":"10.2217/pgs-2023-0243","url":null,"abstract":"<p><p>Whole-exome sequencing (WES) is widely used in clinical settings; however, the exploration of its use in pharmacogenomic analysis remains limited. Our study compared the variant callings for 28 core absorption, distribution, metabolism and elimination genes by WES and array-based technology using clinical trials samples. The results revealed that WES had a positive predictive value of 0.71-0.92 and a sensitivity of single-nucleotide variants between 0.68 and 0.95, compared with array-based technology, for the variants in the commonly targeted regions of the WES and PhamacoScan™ assay. Besides the common variants detected by both assays, WES identified 200-300 exclusive variants per sample, totalling 55 annotated exclusive variants, including important modulators of metabolism such as rs2032582 (<i>ABCB1</i>) and rs72547527 (<i>SULT1A1</i>). This study highlights the potential clinical advantages of using WES to identify a wider range of genetic variations and enabling precision medicine.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140175956","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
Pharmacogenomics for Prader-Willi syndrome: caregiver interest and planned utilization. 普拉德-威利综合征的药物基因组学：护理人员的兴趣和计划利用。
IF 2.1 4区 医学
Pharmacogenomics Pub Date : 2024-03-01 Epub Date: 2024-03-20 DOI: 10.2217/pgs-2023-0189
Yael Bar-Peled, Jessica J Denton, Jaimie L Richards, Donna Brown, Elizabeth Worthey, Theresa V Strong
{"title":"Pharmacogenomics for Prader-Willi syndrome: caregiver interest and planned utilization.","authors":"Yael Bar-Peled, Jessica J Denton, Jaimie L Richards, Donna Brown, Elizabeth Worthey, Theresa V Strong","doi":"10.2217/pgs-2023-0189","DOIUrl":"10.2217/pgs-2023-0189","url":null,"abstract":"<p><p><b>Aim:</b> The study aim was to determine caregiver interest and planned utilization of pharmacogenomic (PGx) results for their child with Prader-Willi syndrome. <b>Methods:</b> Caregivers consented to PGx testing for their child and completed a survey before receiving results. <b>Results:</b> Of all caregivers (n = 48), 93.8% were highly interested in their child's upcoming PGx results. Most (97.9%) planned to share results with their child's medical providers. However, only 47.9% of caregivers were confident providers would utilize the PGx results. <b>Conclusion:</b> Caregivers are interested in utilizing PGx but are uncertain providers will use these results in their child's care. More information about provider comfort with PGx utilization is needed to understand how PGx education would benefit providers and ultimately patients with PGx results.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140175959","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
Ethnic differences in pharmacogenomic variants: a south Asian perspective. 药物基因组变异的种族差异：南亚视角。
IF 2.1 4区 医学
Pharmacogenomics Pub Date : 2024-03-01 Epub Date: 2024-03-21 DOI: 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":null,"pages":null},"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}
引用次数: 0
Targeting RET mutation in medullary thyroid cancer. 针对甲状腺髓样癌的 RET 突变。
IF 2.1 4区 医学
Pharmacogenomics Pub Date : 2024-02-01 Epub Date: 2024-03-07 DOI: 10.2217/pgs-2023-0234
Tarek Assi, Zamzam Tikriti, Annoir Shayya, Rebecca Ibrahim
{"title":"Targeting RET mutation in medullary thyroid cancer.","authors":"Tarek Assi, Zamzam Tikriti, Annoir Shayya, Rebecca Ibrahim","doi":"10.2217/pgs-2023-0234","DOIUrl":"10.2217/pgs-2023-0234","url":null,"abstract":"","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140050118","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
Workforce readiness for pharmacogenomics and key elements for sustainment within the Veterans Health Administration. 退伍军人健康管理局内药物基因组学的人员准备情况和持续发展的关键因素。
IF 2.1 4区 医学
Pharmacogenomics Pub Date : 2024-02-01 Epub Date: 2024-03-05 DOI: 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":null,"pages":null},"PeriodicalIF":2.1,"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}
引用次数: 0
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 2.1 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":"<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":null,"pages":null},"PeriodicalIF":2.1,"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 <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":null,"pages":null},"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":"<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":null,"pages":null},"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
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