首页 > 最新文献

Pharmacogenomics最新文献

英文 中文
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 Q3 PHARMACOLOGY & PHARMACY 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

Objective: This work was designed to describe the knowledge and perceptions of pharmacogenomics (PGx) among pharmacists in the Canadian province of Manitoba. Methods: A 40-item, web-based survey was distributed to pharmacists in Manitoba. Results: 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. Conclusion: Manitoba pharmacists reported positive perceptions toward PGx. However, they are currently underprepared to implement PGx into practice.

目的:本研究旨在描述加拿大马尼托巴省药剂师对药物基因组学 (PGx) 的了解和看法。方法: 向药剂师发放了一份包含 40 个项目的网络调查问卷:向马尼托巴省的药剂师发放了一份包含 40 个项目的网络调查问卷。结果显示在 74 名参与者中,三分之一的人接受过 PGx 方面的教育或培训,12.2% 的人在实践中使用过 PGx 检测结果。参与者对 PGx 检测和常用 PGx 资源(如药物基因组学知识库、临床药物基因组学实施联合会)的自我评价知识水平较低。大多数受访药剂师认为 PGx 可以提高药物疗效(82.4%)或预防药物不良反应(81.1%)。大多数药剂师(91%)希望获得更多有关 PGx 的教育。结论:马尼托巴省的药剂师对 PGx 持积极态度。然而,他们目前还没有做好在实践中实施 PGx 的准备。
{"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":" ","pages":"175-186"},"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 Q3 PHARMACOLOGY & PHARMACY 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

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 (ABCB1) and rs72547527 (SULT1A1). This study highlights the potential clinical advantages of using WES to identify a wider range of genetic variations and enabling precision medicine.

全外显子组测序(WES)已广泛应用于临床,但在药物基因组学分析中的应用探索仍然有限。我们的研究利用临床试验样本,比较了 WES 和基于阵列的技术对 28 个核心吸收、分布、代谢和消除基因的变异调用。结果显示,对于 WES 和 PhamacoScan™ 检测法常用目标区域的变异,WES 的阳性预测值为 0.71-0.92,单核苷酸变异的灵敏度为 0.68-0.95 之间。除了两种检测方法都能检测到的常见变异外,WES 还能为每个样本鉴定出 200-300 个专属变异,共计 55 个注释专属变异,其中包括 rs2032582(ABCB1)和 rs72547527(SULT1A1)等重要的代谢调节因子。这项研究强调了使用 WES 鉴定更广泛的基因变异和实现精准医疗的潜在临床优势。
{"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":" ","pages":"197-206"},"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 Q3 PHARMACOLOGY & PHARMACY 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

Aim: The study aim was to determine caregiver interest and planned utilization of pharmacogenomic (PGx) results for their child with Prader-Willi syndrome. Methods: Caregivers consented to PGx testing for their child and completed a survey before receiving results. Results: 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. Conclusion: 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.

目的:本研究旨在确定照护者对普拉德-威利综合征患儿药物基因组学(PGx)结果的兴趣和计划使用情况。研究方法照顾者同意为其子女进行 PGx 检测,并在收到检测结果前填写一份调查问卷。结果:在所有照顾者(n = 48)中,93.8%的人对孩子即将得到的 PGx 结果非常感兴趣。大多数人(97.9%)计划与孩子的医疗服务提供者分享结果。但是,只有 47.9% 的护理人员相信医疗服务提供者会利用 PGx 结果。结论:照护者对使用 PGx 感兴趣,但不确定医疗服务提供者是否会在其子女的护理中使用这些结果。需要更多有关医疗服务提供者是否愿意使用 PGx 的信息,以了解 PGx 教育将如何使医疗服务提供者受益,并最终使患者受益于 PGx 结果。
{"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":" ","pages":"207-216"},"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 Q3 PHARMACOLOGY & PHARMACY 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":" ","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}
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 Q3 PHARMACOLOGY & PHARMACY 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":" ","pages":"113-115"},"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 1.9 4区 医学 Q3 PHARMACOLOGY & PHARMACY 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

Aim: Understanding barriers and facilitators to pharmacogenomics (PGx) implementation and how to structure a clinical program with the Veterans Health Administration (VA). Materials & methods: 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. Results: 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. Conclusion: HCPs recognize PGx value but are not prepared to implement. Healthcare systems should build system-wide programs for implementation education and support.

目的:了解药物基因组学 (PGx) 实施的障碍和促进因素,以及如何与退伍军人健康管理局 (VA) 一起制定临床计划。材料与方法:对退伍军人健康管理局的 20 家机构进行医疗保健提供者 (HCP) 调查,评估 PGx 知识/接受度,并进行定性访谈,以了解如何以最佳方式设计和维持一项全国性计划。结果:接受调查的 186 名医护人员(回复率为 12%)认为 PGx 可为药物疗效(74.7%)和不良事件(71.0%)提供信息。对知识(43.0%)和实施能力(35.4-43.5%)的信心不足。23 位受访者(回复率 60.5%)支持在全国范围内开展一项计划,以监督退伍军人事务部的教育、咨询和 IT 资源。开处方的保健医生应指导当地的活动。结论:医疗保健人员认识到 PGx 的价值,但尚未做好实施的准备。医疗保健系统应建立全系统的实施教育和支持计划。
{"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}
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 1.9 4区 医学 Q3 PHARMACOLOGY & PHARMACY 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

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.

目的:药物诱发的长 QT 综合征(diLQTS)是许多药物的不良反应,可导致心脏性猝死。心脏离子通道的候选基因变异与 diLQTS 相关,但以往研究的一些局限性妨碍了其临床应用。材料与方法:因此,本研究的目的是在一项大型观察性病例对照研究中评估 KCNE1-D85N、KCNE2-I57T 和 SCN5A-G615E 与 diLQTS 的相关性(6,083 名自我报告的白人患者接受了 27 种不同的高风险 QT 延长药物治疗;12.0% 的患者患有 diLQTS)。研究结果KCNE1-D85N 与 diLQTS 显著相关(调整后的几率比:2.24 [95% CI:1.35-3.58];p = 0.001)。由于小等位基因频率较低,该研究对 KCNE2-I57T 和 SCN5A-G615E 的分析能力不足。结论KCNE1-D85N 是 diLQTS 的一个危险因素,应在未来的临床实践指南中予以考虑。
{"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}
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 Q3 PHARMACOLOGY & PHARMACY 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

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.

目的:CYP2D6 基因具有高度多态性,导致多种临床重要药物的代谢在个体间存在巨大差异。材料与方法:作者利用全基因组序列(N = 1518)研究了印度人 CYP2D6 等位基因的多样性和分布情况。使用致病性评分和分子动力学模拟评估了其功能性后果。结果显示分析结果显示,CYP2D6 等位基因(*86、*7、*111、*112、*113、*99)在人群中具有特异性,其变异和表型频率与全球人群存在显著差异。作者发现,通过准确的 CYP2D6 表型分析,每三个印度人中就有一人可以从精神科药物剂量的改变中获益。分子动力学模拟显示了较大的构象波动,证实了 *86 和 *113 等位基因功能降低的预测。结论研究结果强调了全面的 CYP2D6 分析在帮助精准公共卫生方面的实用性。
{"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}
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 Q3 PHARMACOLOGY & PHARMACY 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

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.

导言:在激素受体阳性/HER2-阴性(HR+/HER2-)转移性乳腺癌(MBC)中,约有40%的患者会发生PIK3CA基因突变,从而选择接受靶向治疗。由于生物标本和检测方法的选择,PIK3CA 状态的检测非常复杂。材料与方法:本研究调查了HR+/HER2- MBC中PIK3CA检测的实际经验。从两家转诊实验室收集了有关 PIK3CA 检测的临床、技术和分子数据。此外,还对涉及 116 家机构的全国性 PIK3CA 调查结果进行了评估。结果:总共有35例MBC发生了PIK3CA突变,突变主要发生在9号外显子(19例;51.4%)和20号外显子(15例;40.5%)。全国范围的调查显示,在常规诊断实践中,各实验室在采样方法、技术评估和PIK3CA分子检测的临床报告签署医疗数字方面存在很大差异。结论:该研究深入揭示了HR+/HER2- MBC中PIK3CA检测的实际常规情况,并强调了预测病理学标准化和网络化的必要性。
{"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}
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 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-01 Epub Date: 2023-12-19 DOI: 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}
引用次数: 0
期刊
Pharmacogenomics
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1