Pharmacogenomics Journal最新文献

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A review of real-world evidence on preemptive pharmacogenomic testing for preventing adverse drug reactions: a reality for future health care 关于预防药物不良反应的先期药物基因组学检测的现实证据综述:未来医疗保健的现实。
IF 2.8 3区 医学
Pharmacogenomics Journal Pub Date : 2024-03-15 DOI: 10.1038/s41397-024-00326-1
Santenna Chenchula, Shubham Atal, Chakradhara Rao S Uppugunduri
{"title":"A review of real-world evidence on preemptive pharmacogenomic testing for preventing adverse drug reactions: a reality for future health care","authors":"Santenna Chenchula, Shubham Atal, Chakradhara Rao S Uppugunduri","doi":"10.1038/s41397-024-00326-1","DOIUrl":"10.1038/s41397-024-00326-1","url":null,"abstract":"Adverse drug reactions (ADRs) are a significant public health concern and a leading cause of hospitalization; they are estimated to be the fourth leading cause of death and increasing healthcare costs worldwide. Carrying a genetic variant could alter the efficacy and increase the risk of ADRs associated with a drug in a target population for commonly prescribed drugs. The use of pre-emptive pharmacogenetic/omic (PGx) testing can improve drug therapeutic efficacy, safety, and compliance by guiding the selection of drugs and/or dosages. In the present narrative review, we examined the current evidence of pre-emptive PGx testing-based treatment for the prevention of ADRs incidence and hospitalization or emergency department visits due to serious ADRs, thus improving patient safety. We then shared our perspective on the importance of preemptive PGx testing in clinical practice for the safe use of medicines and decreasing healthcare costs.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"24 2","pages":"1-6"},"PeriodicalIF":2.8,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10942860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140141108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Network pharmacology prediction, molecular docking and in vitro experiment explored the potential mechanism of Gaoyuan’an capsule in improving hypoxia tolerance 网络药理学预测、分子对接和体外实验探索高元安胶囊改善缺氧耐受性的潜在机制
IF 2.8 3区 医学
Pharmacogenomics Journal Pub Date : 2024-03-14 DOI: 10.1038/s41397-024-00327-0
Tianbo Jin, Xiaoli Liu, Yuhe Wang, Yijin Qi, Xuemei Li, Li Wang, Xue He
{"title":"Network pharmacology prediction, molecular docking and in vitro experiment explored the potential mechanism of Gaoyuan’an capsule in improving hypoxia tolerance","authors":"Tianbo Jin, Xiaoli Liu, Yuhe Wang, Yijin Qi, Xuemei Li, Li Wang, Xue He","doi":"10.1038/s41397-024-00327-0","DOIUrl":"10.1038/s41397-024-00327-0","url":null,"abstract":"Tibetan medicine Gaoyuan’an capsule (GYAC) is widely used to prevent pulmonary edema at high altitude, but the specific mechanism has not been explored. In this study, we analyzed the mechanism of GYAC in hypoxia tolerance, and provided a new idea for the prevention and treatment of altitude disease. The effective components and corresponding targets of GYAC were screened out by the Chinese herbal medicine network database, and the key targets of hypoxia tolerance were retrieved by Genecards, OMIM and PubMed database. Cytoscape 3.7.2 was used to construct GYAC ingredient-target-hypoxia tolerance-related target network. GO function annotation and KEGG enrichment analysis were performed to predict the pathways in which target genes may be involved, and molecular docking was used to verify the binding ability of the compound to target genes. In vitro, the above results were further verified by molecular experiment. We found that GYAC can improve hypoxia tolerance by regulating various target genes, including IL6, IFNG, etc. The main regulatory pathways were HIF-1 signaling pathway. Molecular docking showed that the affinity between luteolin and target genes (IL6, IFNG) were better. In vitro, we observed that hypoxia can inhibit cell viability and promote apoptosis of H9C2 cell. And hypoxia can promote the expression of LDH. After the addition of luteolin, the decrease of cell viability, the increase of cell apoptosis, LDH release and the decrease of mitochondrial membrane potential were inhibited. Besides, inflammatory related factors (IL-6, IL-10, IL-2, IFNG and VEGFA) expression were also inhibited hypoxic cell models. The results of network pharmacology and molecular docking showed that luteolin, a monomeric component of GYAC, played a role in hypoxia tolerance through a variety of target genes, such as IL6, IFNG. What’s more, we have discovered that luteolin can reduce the inflammatory response in cardiac myocytes, thereby alleviating mitochondrial damage, and ultimately enhancing the hypoxia tolerance of H9C2 cardiomyocytes.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"24 2","pages":"1-10"},"PeriodicalIF":2.8,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140128361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Being precise with anticoagulation to reduce adverse drug reactions: are we there yet? 精确抗凝以减少药物不良反应:我们做到了吗?
IF 2.8 3区 医学
Pharmacogenomics Journal Pub Date : 2024-03-05 DOI: 10.1038/s41397-024-00329-y
Benjamin Cross, Richard M. Turner, J. Eunice Zhang, Munir Pirmohamed
{"title":"Being precise with anticoagulation to reduce adverse drug reactions: are we there yet?","authors":"Benjamin Cross, Richard M. Turner, J. Eunice Zhang, Munir Pirmohamed","doi":"10.1038/s41397-024-00329-y","DOIUrl":"10.1038/s41397-024-00329-y","url":null,"abstract":"Anticoagulants are potent therapeutics widely used in medical and surgical settings, and the amount spent on anticoagulation is rising. Although warfarin remains a widely prescribed oral anticoagulant, prescriptions of direct oral anticoagulants (DOACs) have increased rapidly. Heparin-based parenteral anticoagulants include both unfractionated and low molecular weight heparins (LMWHs). In clinical practice, anticoagulants are generally well tolerated, although interindividual variability in response is apparent. This variability in anticoagulant response can lead to serious incident thrombosis, haemorrhage and off-target adverse reactions such as heparin-induced thrombocytopaenia (HIT). This review seeks to highlight the genetic, environmental and clinical factors associated with variability in anticoagulant response, and review the current evidence base for tailoring the drug, dose, and/or monitoring decisions to identified patient subgroups to improve anticoagulant safety. Areas that would benefit from further research are also identified. Validated variants in VKORC1, CYP2C9 and CYP4F2 constitute biomarkers for differential warfarin response and genotype-informed warfarin dosing has been shown to reduce adverse clinical events. Polymorphisms in CES1 appear relevant to dabigatran exposure but the genetic studies focusing on clinical outcomes such as bleeding are sparse. The influence of body weight on LMWH response merits further attention, as does the relationship between anti-Xa levels and clinical outcomes. Ultimately, safe and effective anticoagulation requires both a deeper parsing of factors contributing to variable response, and further prospective studies to determine optimal therapeutic strategies in identified higher risk subgroups.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"24 2","pages":"1-23"},"PeriodicalIF":2.8,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41397-024-00329-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140035375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Pharmacogenetic and clinical risk factors for bevacizumab-related gastrointestinal hemorrhage in prostate cancer patients treated on CALGB 90401 (Alliance) 接受 CALGB 90401(联盟)治疗的前列腺癌患者发生贝伐珠单抗相关消化道出血的药物遗传学和临床风险因素。
IF 2.8 3区 医学
Pharmacogenomics Journal Pub Date : 2024-03-04 DOI: 10.1038/s41397-024-00328-z
Jai N. Patel, Chen Jiang, Kouros Owzar, Daniel L. Hertz, Janey Wang, Flora A. Mulkey, William K. Kelly, Susan Halabi, Yoichi Furukawa, Cameron Lassiter, Susan G. Dorsey, Paula N. Friedman, Eric J. Small, Michael A. Carducci, Michael J. Kelley, Yusuke Nakamura, Michiaki Kubo, Mark J. Ratain, Michael J. Morris, Howard L. McLeod
{"title":"Pharmacogenetic and clinical risk factors for bevacizumab-related gastrointestinal hemorrhage in prostate cancer patients treated on CALGB 90401 (Alliance)","authors":"Jai N. Patel, Chen Jiang, Kouros Owzar, Daniel L. Hertz, Janey Wang, Flora A. Mulkey, William K. Kelly, Susan Halabi, Yoichi Furukawa, Cameron Lassiter, Susan G. Dorsey, Paula N. Friedman, Eric J. Small, Michael A. Carducci, Michael J. Kelley, Yusuke Nakamura, Michiaki Kubo, Mark J. Ratain, Michael J. Morris, Howard L. McLeod","doi":"10.1038/s41397-024-00328-z","DOIUrl":"10.1038/s41397-024-00328-z","url":null,"abstract":"The objective of this study was to discover clinical and pharmacogenetic factors associated with bevacizumab-related gastrointestinal hemorrhage in Cancer and Leukemia Group B (Alliance) 90401. Patients with metastatic castration-resistant prostate cancer received docetaxel and prednisone ± bevacizumab. Patients were genotyped using Illumina HumanHap610-Quad and assessed using cause-specific risk for association between single nucleotide polymorphisms (SNPs) and gastrointestinal hemorrhage. In 1008 patients, grade 2 or higher gastrointestinal hemorrhage occurred in 9.5% and 3.8% of bevacizumab (n = 503) and placebo (n = 505) treated patients, respectively. Bevacizumab (P < 0.001) and age (P = 0.002) were associated with gastrointestinal hemorrhage. In 616 genetically estimated Europeans (n = 314 bevacizumab and n = 302 placebo treated patients), grade 2 or higher gastrointestinal hemorrhage occurred in 9.6% and 2.0% of patients, respectively. One SNP (rs1478947; HR 6.26; 95% CI 3.19–12.28; P = 9.40 × 10−8) surpassed Bonferroni-corrected significance. Grade 2 or higher gastrointestinal hemorrhage rate was 33.3% and 6.2% in bevacizumab-treated patients with the AA/AG and GG genotypes, versus 2.9% and 1.9% in the placebo arm, respectively. Prospective validation of these findings and functional analyses are needed to better understand the genetic contribution to treatment-related gastrointestinal hemorrhage.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"24 2","pages":"1-8"},"PeriodicalIF":2.8,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10912014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140029613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Upregulation of p300 in paclitaxel-resistant TNBC: implications for cell proliferation via the PCK1/AMPK axis 紫杉醇耐药 TNBC 中 p300 的上调:通过 PCK1/AMPK 轴对细胞增殖的影响。
IF 2.8 3区 医学
Pharmacogenomics Journal Pub Date : 2024-02-20 DOI: 10.1038/s41397-024-00324-3
Peng-Wei Zhao, Jia-Xian Cui, Xiu-Mei Wang
{"title":"Upregulation of p300 in paclitaxel-resistant TNBC: implications for cell proliferation via the PCK1/AMPK axis","authors":"Peng-Wei Zhao, Jia-Xian Cui, Xiu-Mei Wang","doi":"10.1038/s41397-024-00324-3","DOIUrl":"10.1038/s41397-024-00324-3","url":null,"abstract":"To explore the role of p300 in the context of paclitaxel (PTX) resistance in triple-negative breast cancer (TNBC) cells, focusing on its interaction with the phosphoenolpyruvate carboxykinase 1 (PCK1)/adenosine monophosphate-activated protein kinase (AMPK) pathway. The expression of p300 and PCK1 at the messenger ribonucleic acid (mRNA) level was detected using a quantitative polymerase chain reaction. The GeneCards and GEPIA databases were used to investigate the relationship between p300 and PCK1. The MDA-MB-231/PTX cell line, known for its PTX resistance, was chosen to understand the specific role of p300 in such cells. The Lipofectamine™ 3000 reagent was used to transfer the p300 small interfering RNA and the overexpression of PCK1 plasmid into MDA-MB-231/PTX. The expression levels of p300, PCK1, 5′AMPK and phosphorylated AMPK (p-AMPK) were determined using the western blot test. In TNBC cancer tissue, the expression of p300 was increased compared with TNBC paracancerous tissue (P < 0.05). In the MDA-MB-231 cell line of TNBC, the expression of p300 was lower than in the PTX-resistant TNBC cells (MDA-MB-231/PTX) (P < 0.05). The PCK1 expression was decreased in the TNBC cancer tissue compared with TNBC paracancerous tissue, and the PCK1 expression was reduced in MDA-MB-231/PTX than in MDA-MB-231 (P < 0.05) indicating that PCK1 was involved in the resistance function. Additionally, p-AMPK was decreased in MDA-MB-231/PTX compared with MDA-MB-231 (P < 0.05). The adenosine triphosphate (ATP) level was also detected and was significantly lower in MDA-MB-231/PTX than in MDA-MB-231 (P < 0.05). Additionally, cell proliferation increased significantly in MDA-MB-231/PTX at 48 and 72 h (P < 0.05) suggesting that MDA-MB-231/PTX cells obtained the resistance function which was associated with AMPK and ATP level. When p300 was inhibited, p-AMPK and ATP levels elevated in MDA-MB-231/PTX (P < 0.05). When PCK1 was suppressed, the ATP consumption rate decreased, and cell proliferation increased (P < 0.05). However, there were no changes in p300. In MDA-MB-231/PTX, p300 can inhibit p-AMPK and ATP levels by inhibiting PCK1 expression. Our findings suggest that targeting p300 could modulate the PCK1/AMPK axis, offering a potential therapeutic avenue for overcoming PTX resistance in TNBC.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"24 2","pages":"1-9"},"PeriodicalIF":2.8,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139914063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Composite CYP3A (CYP3A4 and CYP3A5) phenotypes and influence on tacrolimus dose adjusted concentrations in adult heart transplant recipients 成人心脏移植受者的复合 CYP3A(CYP3A4 和 CYP3A5)表型及其对他克莫司剂量调整浓度的影响。
IF 2.8 3区 医学
Pharmacogenomics Journal Pub Date : 2024-02-15 DOI: 10.1038/s41397-024-00325-2
Michelle Liu, Savine Hernandez, Christina L. Aquilante, Kimberly M. Deininger, Joann Lindenfeld, Kelly H. Schlendorf, Sara L. Van Driest
{"title":"Composite CYP3A (CYP3A4 and CYP3A5) phenotypes and influence on tacrolimus dose adjusted concentrations in adult heart transplant recipients","authors":"Michelle Liu, Savine Hernandez, Christina L. Aquilante, Kimberly M. Deininger, Joann Lindenfeld, Kelly H. Schlendorf, Sara L. Van Driest","doi":"10.1038/s41397-024-00325-2","DOIUrl":"10.1038/s41397-024-00325-2","url":null,"abstract":"CYP3A5 genetic variants are associated with tacrolimus metabolism. Controversy remains on whether CYP3A4 increased [*1B (rs2740574), *1 G (rs2242480)] and decreased function [*22 (rs35599367)] genetic variants provide additional information. This retrospective cohort study aims to address whether tacrolimus dose-adjusted trough concentrations differ between combined CYP3A (CYP3A5 and CYP3A4) phenotype groups. Heart transplanted patients (n = 177, between 2008 and 2020) were included and median age was 54 years old. Significant differences between CYP3A phenotype groups in tacrolimus dose-adjusted trough concentrations were found in the early postoperative period and continued to 6 months post-transplant. In CYP3A5 nonexpressers, carriers of CYP3A4*1B or *1 G variants (Group 3) compared to CYP3A4*1/*1 (Group 2) patients were found to have lower tacrolimus dose-adjusted trough concentrations at 2 months. In addition, significant differences were found among CYP3A phenotype groups in the dose at discharge and time to therapeutic range while time in therapeutic range was not significantly different. A combined CYP3A phenotype interpretation may provide more nuanced genotype-guided TAC dosing in heart transplant recipients.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"24 2","pages":"1-8"},"PeriodicalIF":2.8,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139742708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
The pharmacogenetics of tacrolimus in renal transplant patients: association with tremors, new-onset diabetes and other clinical events 肾移植患者他克莫司的药物遗传学:与震颤、新发糖尿病和其他临床事件的关系
IF 2.8 3区 医学
Pharmacogenomics Journal Pub Date : 2024-01-22 DOI: 10.1038/s41397-024-00323-4
Amani Abderahmene, Yassine khalij, Amira Moussa, Meriam Ammar, Amel Ellouz, Dorra Amor, Houwaida Abbes, Mohamed Rayen Ganouni, Wissal Sahtout, Saoussen Chouchene, Asma omezzine, Dorsaf zellama, Ali Bouslama
{"title":"The pharmacogenetics of tacrolimus in renal transplant patients: association with tremors, new-onset diabetes and other clinical events","authors":"Amani Abderahmene, Yassine khalij, Amira Moussa, Meriam Ammar, Amel Ellouz, Dorra Amor, Houwaida Abbes, Mohamed Rayen Ganouni, Wissal Sahtout, Saoussen Chouchene, Asma omezzine, Dorsaf zellama, Ali Bouslama","doi":"10.1038/s41397-024-00323-4","DOIUrl":"10.1038/s41397-024-00323-4","url":null,"abstract":"Our study is the first study to investigate the effect of SNPs in CYP3A5, CYP3A4, ABCB1 and POR genes on the incidence of tremors, nephrotoxicity, and diabetes mellitus. A total of 223 renal transplant patients receiving tacrolimus and mycophenolate mofetil (MMF) were recruited. Both adults and children patients participated in the study. Genotyping was performed using PROFLEX-PCR followed by RFLP. MPA and tacrolimus plasma concentrations were measured by immunoassay. The AUC0-12h of MMF was estimated by a Bayesian method. We found a statistically significant association between the CYP3A5*3 and CYP3A4*1B genotypes and the tacrolimus exposure. We found a lower occurrence of nephrotoxicity (p = 0.03), tremor (p = 0.01), and new-onset diabetes (p = 0.002) associated with CYP3A5*1 allele. The CYP3A4*1B allele was significantly associated with a lower occurrence of new-onset diabetes (p = 0.026). The CYP3A5*1 allele was significantly associated with an increased risk of acute and chronic rejection (p = 0.03 and p < 0.001, respectively). Our results support the usefulness of tacrolimus pharmacokinetics in pre-kidney transplant assessments.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"24 1","pages":"1-6"},"PeriodicalIF":2.8,"publicationDate":"2024-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139516002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Pharmacogenomic biomarker information on drug labels of the Spanish Agency of Medicines and Sanitary products: evaluation and comparison with other regulatory agencies 西班牙药品和卫生产品管理局药品标签上的药物基因组生物标记信息:评估以及与其他监管机构的比较
IF 2.8 3区 医学
Pharmacogenomics Journal Pub Date : 2024-01-17 DOI: 10.1038/s41397-023-00321-y
María Estévez-Paredes, M. Carmen Mata-Martín, Fernando de Andrés, Adrián LLerena
{"title":"Pharmacogenomic biomarker information on drug labels of the Spanish Agency of Medicines and Sanitary products: evaluation and comparison with other regulatory agencies","authors":"María Estévez-Paredes, M. Carmen Mata-Martín, Fernando de Andrés, Adrián LLerena","doi":"10.1038/s41397-023-00321-y","DOIUrl":"10.1038/s41397-023-00321-y","url":null,"abstract":"This work aimed to analyse the pharmacogenetic information in the Spanish Drug Regulatory Agency (AEMPS) Summary of Products Characteristics (SmPC), evaluating the presence of pharmacogenetic biomarkers, as well as the associated recommendations. A total of 55.4% of the 1891 drug labels reviewed included information on pharmacogenetic biomarker(s). Pharmacogenomic information appears most frequently in the “antineoplastic and immunomodulating agents”, “nervous system”, and “cardiovascular system” Anatomical Therapeutic Chemical groups. A total of 509 different pharmacogenetic biomarkers were found, of which CYP450 enzymes accounted for almost 34% of the total drug-biomarker associations evaluated. A total of 3679 drug–biomarker pairs were identified, 102 of which were at the 1A level (PharmGKB® classification system), and 33.33% of these drug-pharmacogenetic biomarker pairs were assigned to “actionable PGx”, 12.75% to “informative PGx”, 4.9% to “testing recommended”, and 4.9% to “testing required”. The rate of coincidence in the assigned PGx level of recommendation between the AEMPS and regulatory agencies included in the PharmGKB® Drug Label Annotations database (i.e., the FDA, EMA, SWISS Medic, PMDA, and HCSC) ranged from 45% to 65%, being ‘actionable level’ the most frequent. On the other hand, discrepancies between agencies did not exceed 35%. This study highlights the presence of relevant pharmacogenetic information on Spanish drug labels, which would help avoid interactions, toxicity, or lack of treatment efficacy.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"24 1","pages":"1-11"},"PeriodicalIF":2.8,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139483775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Integrating rare genetic variants into DPYD pharmacogenetic testing may help preventing fluoropyrimidine-induced toxicity 将罕见基因变异纳入 DPYD 药物基因检测,可能有助于预防氟嘧啶引起的毒性。
IF 2.8 3区 医学
Pharmacogenomics Journal Pub Date : 2024-01-12 DOI: 10.1038/s41397-023-00322-x
Romain Larrue, Sandy Fellah, Benjamin Hennart, Naoual Sabaouni, Nihad Boukrout, Cynthia Van der Hauwaert, Clément Delage, Meyling Cheok, Michaël Perrais, Christelle Cauffiez, Delphine Allorge, Nicolas Pottier
{"title":"Integrating rare genetic variants into DPYD pharmacogenetic testing may help preventing fluoropyrimidine-induced toxicity","authors":"Romain Larrue, Sandy Fellah, Benjamin Hennart, Naoual Sabaouni, Nihad Boukrout, Cynthia Van der Hauwaert, Clément Delage, Meyling Cheok, Michaël Perrais, Christelle Cauffiez, Delphine Allorge, Nicolas Pottier","doi":"10.1038/s41397-023-00322-x","DOIUrl":"10.1038/s41397-023-00322-x","url":null,"abstract":"Variability in genes involved in drug pharmacokinetics or drug response can be responsible for suboptimal treatment efficacy or predispose to adverse drug reactions. In addition to common genetic variations, large-scale sequencing studies have uncovered multiple rare genetic variants predicted to cause functional alterations in genes encoding proteins implicated in drug metabolism, transport and response. To understand the functional importance of rare genetic variants in DPYD, a pharmacogene whose alterations can cause severe toxicity in patients exposed to fluoropyrimidine-based regimens, massively parallel sequencing of the exonic regions and flanking splice junctions of the DPYD gene was performed in a series of nearly 3000 patients categorized according to pre-emptive DPD enzyme activity using the dihydrouracil/uracil ([UH2]/[U]) plasma ratio as a surrogate marker of DPD activity. Our results underscore the importance of integrating next-generation sequencing-based pharmacogenomic interpretation into clinical decision making to minimize fluoropyrimidine-based chemotherapy toxicity without altering treatment efficacy.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"24 1","pages":"1-9"},"PeriodicalIF":2.8,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10786722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139432949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Cytochrome P450-2D6 activity in people with codeine use disorder 可待因使用障碍患者的细胞色素P450-2D6活性。
IF 2.8 3区 医学
Pharmacogenomics Journal Pub Date : 2023-11-09 DOI: 10.1038/s41397-023-00319-6
Mark R. C. Daglish, Sarah R. Reilly, Sam Mostafa, Cameron Edwards, Thomas M. O’Gorman, Jeremy S. Hayllar
{"title":"Cytochrome P450-2D6 activity in people with codeine use disorder","authors":"Mark R. C. Daglish, Sarah R. Reilly, Sam Mostafa, Cameron Edwards, Thomas M. O’Gorman, Jeremy S. Hayllar","doi":"10.1038/s41397-023-00319-6","DOIUrl":"10.1038/s41397-023-00319-6","url":null,"abstract":"Compound-analgesics containing codeine (CACC) have been a common source of codeine for people seeking opioid replacement therapy (ORT) for codeine use disorder (CUD). Our previous work demonstrated no relationship between pre-treatment CACC and ORT buprenorphine doses; we hypothesised that CYP2D6 activity would partially account for this disconnection. One hundred six participants with CUD were compared to a published population sample of 5408 Australian patients. Mean age of participants with CUD at treatment entry was 35 years, with mean 6.1 years duration of CUD. Mean codeine dose was 660 mg/day (range 40–2700 mg). Mean calculated CYP2D6 activity scores were significantly higher in the codeine group (CUD 1.65 + 0.63 vs. Gen pop 1.39 + 0.65, Wilcoxon W = 347,001, p < 0.001). Pre-treatment CACC dose weakly predicted sublingual buprenorphine doses overall; there was a stronger relationship within ultrarapid metabolisers. While normal and ultrarapid metabolisers of codeine were more likely to have a diagnosis of CUD, poor or intermediate CYP2D6 metaboliser status may protect against CUD.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"23 6","pages":"195-200"},"PeriodicalIF":2.8,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10661737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71523396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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