Pharmacogenomics最新文献_第2页

Pharmacogenomic variants affecting efficacy and safety of medicines acting on central nervous system among Sri Lankans. 影响斯里兰卡人中枢神经系统药物疗效和安全性的药物基因组变异。

IF 1.9 4区医学

Pharmacogenomics Pub Date : 2025-09-13 DOI: 10.1080/14622416.2025.2558498

Priyanga Ranasinghe, Charindie Peiris, Hajanthy Jeyapragasam, Nirmala D Sirisena, D P Bhagya Hendalage, Vajira H W Dissanayake

{"title":"Pharmacogenomic variants affecting efficacy and safety of medicines acting on central nervous system among Sri Lankans.","authors":"Priyanga Ranasinghe, Charindie Peiris, Hajanthy Jeyapragasam, Nirmala D Sirisena, D P Bhagya Hendalage, Vajira H W Dissanayake","doi":"10.1080/14622416.2025.2558498","DOIUrl":"https://doi.org/10.1080/14622416.2025.2558498","url":null,"abstract":"Background: Ensuring the efficacy and safety of medicines acting on the central nervous system (CNS) remains a challenge due to their complex pharmacokinetics and inter-individual variability in response. We describe the frequencies of pharmacogenomic variants affecting CNS drug metabolism in a Sri Lankan population.Methods: Pharmacogenomic data pertaining to genes of interest were obtained from the Pharmacogenomics Knowledgebase database. Pharmacokinetically relevant cytochrome P450 isoforms were selected. Their frequencies in Sri Lankans were obtained from an anonymized database derived from 690 participants, from the Human Genetics Unit, Faculty of Medicine, University of Colombo. Minor allele frequencies (MAFs) of these variants were calculated and compared with other populations.Results: MAFs of CYP2C19 rs4244285, CYP2D6 rs16947, CYP2D6 rs1058164, CYP2D6 rs1135840, and CYP2B6 rs3745274 were notably high at 40.9% (95%CI:38.3-43.5), 58.0% (95%CI:55.3-60.6), 43.8% (95%CI:41.1-46.4), 44.1% (95%CI:41.5-46.8), and 39.8% (95%CI:37.2-42.4), respectively. MAFs of CYP2C9 rs72558189, CYP2C19 rs4244285, CYP2D6 rs77913725, CYP2D6 rs1135828, and CYP2B6 rs3745274 recorded the highest in Sri Lankans when compared to all other populations. A lower prevalence was noted in MAFs of CYP2D6 rs1065852, CYP2D6 rs16947, and CYP2D6 rs28371706.Conclusion: Sri Lankans exhibit an increased susceptibility to adverse reactions with common antidepressants, antipsychotics, and analgesics and reduced efficacy to opioid analgesics. These findings highlight the need for population-specific pharmacogenomic guidelines.","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"1-9"},"PeriodicalIF":1.9,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145054974","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

Impact of ABCB1 gene polymorphism on clopidogrel plasma concentration and cardiovascular events in post-PCI patients. ABCB1基因多态性对pci术后患者氯吡格雷血药浓度及心血管事件的影响

IF 1.9 4区医学

Pharmacogenomics Pub Date : 2025-07-21 DOI: 10.1080/14622416.2025.2534325

Abdur Razaq, Waheed Iqbal, Syed Tahir Shah, Muhammad Abdur Rauf, Nasser M Aldekhail, Filip Van Nieuwerburgh, Sami Siraj

{"title":"Impact of ABCB1 gene polymorphism on clopidogrel plasma concentration and cardiovascular events in post-PCI patients.","authors":"Abdur Razaq, Waheed Iqbal, Syed Tahir Shah, Muhammad Abdur Rauf, Nasser M Aldekhail, Filip Van Nieuwerburgh, Sami Siraj","doi":"10.1080/14622416.2025.2534325","DOIUrl":"https://doi.org/10.1080/14622416.2025.2534325","url":null,"abstract":"Aim: This study investigated the impact of ABCB1 gene polymorphisms on clopidogrel absorption and therapeutic response by analyzing plasma levels of the clopidogrel carboxylic acid metabolite (CAM), and cardiovascular events (CVEs) in patients undergoing percutaneous coronary intervention (PCI).Methods: A prospective cohort study of 264 post-PCI patients was conducted in Peshawar, Pakistan. CVEs over 12 months were recorded. Plasma concentrations of CAM were measured by high-performance liquid chromatography (HPLC), while the ABCB1 gene (rs1045642) was genotyped by Sanger sequencing to determine associations between genetic variants, CAM levels, and clinical outcomes.Results: The study documented 54 CVEs, including 13 deaths, 6 stent thromboses, 10 recurrent myocardial infarctions, 23 ischemic events requiring hospitalization, and 2 strokes. The analysis showed that 31.1% of patients had subtherapeutic CAM levels ( <2000 ng/ml), while 68.9% had therapeutic levels. Genetic analysis identified 65% as poor absorbers (CT/TT genotypes) and 35% as good absorbers (CC genotype), while CAM levels were significantly associated with the CT/TT genotype (p < 0.005).Conclusion: This study linking ABCB1 variation to CAM concentration and therapeutic outcomes. There was a significant association between ABCB1 variants and CAM concentrations. However, no association was found between ABCB1 polymorphisms and CVEs.","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"1-8"},"PeriodicalIF":1.9,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675442","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

Evidence level for pharmacogenetic testing in antidepressant treatment: a systematic review. 抗抑郁药治疗药物遗传学检测的证据水平：一项系统综述。

IF 1.9 4区医学

Pharmacogenomics Pub Date : 2025-05-01 Epub Date: 2025-08-03 DOI: 10.1080/14622416.2025.2541402

Emytis Tavakoli, Leen Magarbeh, Samar Elsheikh, Amy Y Zhang, Arun K Tiwari, Clement C Zai, Martin Kronenbuerger, Heike Weber, Maike Scherf-Clavel, Stefan Unterecker, Jürgen Deckert, Daniel J Müller

{"title":"Evidence level for pharmacogenetic testing in antidepressant treatment: a systematic review.","authors":"Emytis Tavakoli, Leen Magarbeh, Samar Elsheikh, Amy Y Zhang, Arun K Tiwari, Clement C Zai, Martin Kronenbuerger, Heike Weber, Maike Scherf-Clavel, Stefan Unterecker, Jürgen Deckert, Daniel J Müller","doi":"10.1080/14622416.2025.2541402","DOIUrl":"10.1080/14622416.2025.2541402","url":null,"abstract":"Rationale: Preemptive pharmacogenetic (PGx) testing offers a promising approach to personalized antidepressant treatment by identifying genetic variations influencing drug metabolism. By focusing on CYP2D6 and CYP2C19 genes, this strategy aims to improve treatment response, minimize adverse effects, and optimize dosing in patients with depression.Objectives and methods: This systematic review evaluates the effectiveness of preemptive PGx testing, primarily for CYP2D6 and CYP2C19, in enhancing antidepressant treatment outcomes. A comprehensive search of databases, including PubMed and Embase, was conducted to identify relevant studies. The review included randomized controlled trials and meta-analyses that assessed PGx testing in relation to treatment response and remission. Data on clinical outcomes were extracted and analyzed.Results: PGx testing led to improved antidepressant response rates and remission at 8- and 12-week follow-ups compared to treatment-as-usual (TAU). However, where data were available, benefits were less pronounced after six months of follow-up. The findings suggest that PGx testing plays an important role in achieving earlier remission, while TAU requires a longer time to achieve remission.Conclusion: Preemptive pharmacogenetic testing for CYP2D6 and CYP2C19 could enhance early antidepressant treatment outcomes, offering a valuable tool for personalized medicine. Further research is required to explore implementation challenges in diverse clinical settings.","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"295-309"},"PeriodicalIF":1.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12427529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144776000","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 polymorphism associated with non-response to therapy in inflammatory bowel disease patients: a review. 与炎症性肠病患者治疗无反应相关的基因多态性：综述

IF 1.9 4区医学

Pharmacogenomics Pub Date : 2025-05-01 Epub Date: 2025-08-16 DOI: 10.1080/14622416.2025.2547561

Thinagary Jegathesan, Syaratul Dalina Yusoff, Nor Asyikin Mohd Tahir

引用次数: 0

The pharmacogenetics of rosuvastatin and implications for treatment: a systematic review. 瑞舒伐他汀的药物遗传学及其治疗意义：一项系统综述。

IF 1.9 4区医学

Pharmacogenomics Pub Date : 2025-05-01 Epub Date: 2025-08-21 DOI: 10.1080/14622416.2025.2547565

Eva González-Iglesias, Jesús Novalbos, Francisco Abad-Santos

{"title":"The pharmacogenetics of rosuvastatin and implications for treatment: a systematic review.","authors":"Eva González-Iglesias, Jesús Novalbos, Francisco Abad-Santos","doi":"10.1080/14622416.2025.2547565","DOIUrl":"10.1080/14622416.2025.2547565","url":null,"abstract":"Introduction: Rosuvastatin has become a good choice in the statin group because it has shown greater efficacy in reducing lipid levels than other statins, allowing patients to reach their therapeutic goal more quickly. To date, research has shown a broad relationship between the kinetics and efficacy of this drug and the phenotype of two transporters, OATP1B1 and BCRP, encoded by SLCO1B1 and ABCG2 genes. However, there are many other genes whose variation may also affect the treatment.Objective: To conduct a systematic review including all information on the kinetics, measured by AUC and Cmax parameters; efficacy, by reduction in lipid levels and carotid intima-media thickness; and safety of rosuvastatin, by the occurrence of adverse events.Methods: A search of the published literature was conducted in PubMed using the term \"rosuvastatin AND pharmacogenetics\" (PROSPERO code: CRD420251041953).Results: A total of 37 articles were included, investigating 40 genes.Conclusions: The importance of ABCG2 in drug kinetics and efficacy and of SLCO1B1 in kinetics is confirmed, as is the possible association of CYP3A5 with efficacy and safety and of APOC1 with efficacy. There are also positive results for other genes that should be studied further to confirm their association with rosuvastatin.","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"311-329"},"PeriodicalIF":1.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12427528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144964808","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

Variation in the ABC transporter genes and association with clinical outcomes in colorectal cancer: a brief review. 结直肠癌ABC转运蛋白基因变异及其与临床预后的关系：综述

IF 1.9 4区医学

Pharmacogenomics Pub Date : 2025-05-01 Epub Date: 2025-07-18 DOI: 10.1080/14622416.2025.2534319

Zari Salahud Din, Maryam Saqib, Sehrish Zafar, Nyla Munawar, Sagheer Ahmed

引用次数: 0

Opportunistic analysis of clinically actionable DPYD gene variants in a germline testing cohort in India. 机会分析临床可操作的DPYD基因变异在种系检测队列在印度。

IF 1.9 4区医学

Pharmacogenomics Pub Date : 2025-05-01 Epub Date: 2025-08-14 DOI: 10.1080/14622416.2025.2547563

Rajdeep Raha, Rahul C Bhoyar, Ranendra Pratap Biswal, Radhika Venkatakrishnan, Prashant Rai, Eshaa Umashankar, Pooja Mahesh Kulkarni, Sridhar Sivasubbu, Vinod Scaria, Bani Jolly

{"title":"Opportunistic analysis of clinically actionable DPYD gene variants in a germline testing cohort in India.","authors":"Rajdeep Raha, Rahul C Bhoyar, Ranendra Pratap Biswal, Radhika Venkatakrishnan, Prashant Rai, Eshaa Umashankar, Pooja Mahesh Kulkarni, Sridhar Sivasubbu, Vinod Scaria, Bani Jolly","doi":"10.1080/14622416.2025.2547563","DOIUrl":"10.1080/14622416.2025.2547563","url":null,"abstract":"Aims: Dihydropyrimidine dehydrogenase (DPYD) plays a critical role in the metabolism of fluoropyrimidine-based chemotherapies such as 5-fluorouracil (5-FU), capecitabine, and tegafur. Genetic variants in DPYD can lead to partial or complete enzyme deficiency, resulting in toxic accumulation of these drugs and severe, sometimes fatal, adverse reactions.Materials & methods: Whole‑exome sequencing data from 1,612 individuals were analyzed for DPYD variants. Variants were classified as decreased, no function, or potentially deleterious. Comparative allele frequency analysis was performed using global population datasets to identify inter-population differences.Results and conclusion: A total of 95 individuals (5.3%) carried at least one decreased or no function DPYD variant, indicating a significant prevalence of clinically actionable genotypes in this Indian cohort. The most frequent variant, c.1236 G > A (HapB3), was found in 53 individuals (3.28%), supporting its relevance in the Indian population. Comparative analysis revealed distinct population patterns and novel variants not captured in current guidelines. These results support the urgency in implementing preemptive DPYD genotyping to avoid adverse drug reactions and further studies to gather evidence on rare and novel variants in the Indian population. To the best of our knowledge, this is the largest population analysis of DPYD variants from India.","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"231-236"},"PeriodicalIF":1.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12427532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855970","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

Pharmacogenomics of buprenorphine - a narrative review. 丁丙诺啡的药物基因组学研究综述。

IF 1.9 4区医学

Pharmacogenomics Pub Date : 2025-05-01 Epub Date: 2025-09-05 DOI: 10.1080/14622416.2025.2546770

Lakshmi Aravindan, Sanjana Velu, Inesh Sivam, Sahana Sivam, Pooja S Tallapaneni, Ruthie Ressler, Michael Marks, Raman Venkataramanan, Rupa Radhakrishnan, Senthilkumar Sadhasivam

{"title":"Pharmacogenomics of buprenorphine - a narrative review.","authors":"Lakshmi Aravindan, Sanjana Velu, Inesh Sivam, Sahana Sivam, Pooja S Tallapaneni, Ruthie Ressler, Michael Marks, Raman Venkataramanan, Rupa Radhakrishnan, Senthilkumar Sadhasivam","doi":"10.1080/14622416.2025.2546770","DOIUrl":"10.1080/14622416.2025.2546770","url":null,"abstract":"Buprenorphine, a semi-synthetic opioid, is used to treat Opioid Use Disorder (OUD) and as an analgesic. Buprenorphine's benefits over other opioids include longer duration of action, lower abuse potential, and a ceiling effect to serious adverse effects such as respiratory depression. This is a literature review of gene variants affecting the pharmacokinetics and pharmacodynamics of buprenorphine from databases, such as PubMed. Genetic polymorphisms related to metabolism and receptor binding of buprenorphine can alter the pharmacokinetics and response to buprenorphine. Specifically, genetic variants in CYP3A4, UGT2B7, OPRM1, PDYN, and SLC6A3 may affect metabolism and clinical response to buprenorphine. There is strong evidence linking polymorphism in Cytochrome P450 3A4 (CYP3A4) and UDP-Glucuronosyltransferase-2B7 (UGT2B7), enzymes involved in buprenorphine metabolism, with dosing requirements, treatment of OUD, and pain relief. Response to buprenorphine, an effective treatment for opioid use disorder and pain management, differs significantly based on several human genetic variations. However, there is currently insufficient evidence for the clinical significance of individualized treatment of buprenorphine based on genetic variants. Therefore, it is crucial that future research should prioritize evaluating the feasibility and clinical significance of individualized risk predictions and personalized dosing of buprenorphine.","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"263-270"},"PeriodicalIF":1.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12427432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001239","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 graft-versus-host disease: a path to personalized medicine. 移植物抗宿主病的药物遗传学：个性化医疗的途径。

IF 1.9 4区医学

Pharmacogenomics Pub Date : 2025-05-01 Epub Date: 2025-08-07 DOI: 10.1080/14622416.2025.2541404

Piotr Łacina, Jagoda Siemaszko, Katarzyna Bogunia-Kubik

引用次数: 0

From bench to bedside: a spotlight on pharmacogenomics at Nemours Children's Health. 从实验室到床边：内穆尔儿童健康中心药物基因组学聚焦。

IF 1.9 4区医学

Pharmacogenomics Pub Date : 2025-05-01 Epub Date: 2025-07-29 DOI: 10.1080/14622416.2025.2539061

Kelsey J Cook, Nathan D Seligson, Benjamin Q Duong, Vicky L Funanage, Susan M Kirwin, Edward B Mougey, Stephen Lawless, David West, Pamela H Arn, Kathryn V Blake

{"title":"From bench to bedside: a spotlight on pharmacogenomics at Nemours Children's Health.","authors":"Kelsey J Cook, Nathan D Seligson, Benjamin Q Duong, Vicky L Funanage, Susan M Kirwin, Edward B Mougey, Stephen Lawless, David West, Pamela H Arn, Kathryn V Blake","doi":"10.1080/14622416.2025.2539061","DOIUrl":"10.1080/14622416.2025.2539061","url":null,"abstract":"Nemours Children's Health (NCH) is a large, multi-state pediatric health system in the United States with hospitals and outpatient locations across Delaware, New Jersey, Pennsylvania, and Florida. NCH has maintained consistent effort in pharmacogenomic (PGx) research through the Center for Pharmacogenomics and Translational Research since 2003. In 2018, NCH funded the development of a dedicated Clinical Pharmacogenomics Service (CPGxS) to support PGx testing and return of results across the NCH enterprise. The CPGxS consultant-based service provides clinical PGx testing and supports PGx-focused research. Over the past seven years, the CPGxS has developed an in-house PGx testing platform, integrated a PGx clinical decision support (CDS) system into the electronic medical record (EHR), established a comprehensive consultant clinic, and provided a broad variety of education opportunities for providers, patients, and trainees. In this institutional profile, we highlight the development of a PGx program and related efforts across a multi-state pediatric-specific healthcare system.","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"223-229"},"PeriodicalIF":1.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12427439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732745","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