Pharmacogenomics Journal最新文献_第9页

Influence of UGT1A1 and SLC22A6 polymorphisms on the population pharmacokinetics and pharmacodynamics of raltegravir in HIV-infected adults: a NEAT001/ANRS143 sub-study UGT1A1 和 SLC22A6 多态性对艾滋病毒感染成人中拉替拉韦群体药代动力学和药效学的影响：NEAT001/ANRS143 子研究

IF 2.8 3区医学

Pharmacogenomics Journal Pub Date : 2022-10-20 DOI: 10.1038/s41397-022-00293-5

Rohan Gurjar, Laura Dickinson, Daniel Carr, Wolfgang Stöhr, Stefano Bonora, Andrew Owen, Antonio D’Avolio, Adam Cursley, Nathalie De Castro, Gerd Fätkenheuer, Linos Vandekerckhove, Giovanni Di Perri, Anton Pozniak, Christine Schwimmer, François Raffi, Marta Boffito, the NEAT001/ANRS143 Study Group

{"title":"Influence of UGT1A1 and SLC22A6 polymorphisms on the population pharmacokinetics and pharmacodynamics of raltegravir in HIV-infected adults: a NEAT001/ANRS143 sub-study","authors":"Rohan Gurjar, Laura Dickinson, Daniel Carr, Wolfgang Stöhr, Stefano Bonora, Andrew Owen, Antonio D’Avolio, Adam Cursley, Nathalie De Castro, Gerd Fätkenheuer, Linos Vandekerckhove, Giovanni Di Perri, Anton Pozniak, Christine Schwimmer, François Raffi, Marta Boffito, the NEAT001/ANRS143 Study Group","doi":"10.1038/s41397-022-00293-5","DOIUrl":"10.1038/s41397-022-00293-5","url":null,"abstract":"Using concentration-time data from the NEAT001/ARNS143 study (single sample at week 4 and 24), we determined raltegravir pharmacokinetic parameters using nonlinear mixed effects modelling (NONMEM v.7.3; 602 samples from 349 patients) and investigated the influence of demographics and SNPs (SLC22A6 and UGT1A1) on raltegravir pharmacokinetics and pharmacodynamics. Demographics and SNPs did not influence raltegravir pharmacokinetics and no significant pharmacokinetic/pharmacodynamic relationships were observed. At week 96, UGT1A1*28/*28 was associated with lower virological failure (p = 0.012), even after adjusting for baseline CD4 count (p = 0.048), but not when adjusted for baseline HIV-1 viral load (p = 0.082) or both (p = 0.089). This is the first study to our knowledge to assess the influence of SNPs on raltegravir pharmacodynamics. The lack of a pharmacokinetic/pharmacodynamic relationship is potentially an artefact of raltegravir’s characteristic high inter and intra-patient variability and also suggesting single time point sampling schedules are inadequate to thoroughly assess the influence of SNPs on raltegravir pharmacokinetics.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"23 1","pages":"14-20"},"PeriodicalIF":2.8,"publicationDate":"2022-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9584256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9477454","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

Do genetics contribute to TNF inhibitor response prediction in Psoriatic Arthritis? 遗传是否有助于预测银屑病关节炎患者对 TNF 抑制剂的反应？

IF 2.8 3区医学

Pharmacogenomics Journal Pub Date : 2022-10-15 DOI: 10.1038/s41397-022-00290-8

Philippa D. K. Curry, Andrew P. Morris, Anne Barton, James Bluett

{"title":"Do genetics contribute to TNF inhibitor response prediction in Psoriatic Arthritis?","authors":"Philippa D. K. Curry, Andrew P. Morris, Anne Barton, James Bluett","doi":"10.1038/s41397-022-00290-8","DOIUrl":"10.1038/s41397-022-00290-8","url":null,"abstract":"Psoriatic arthritis (PsA) is a heterogeneous chronic musculoskeletal disease, affecting up to 30% of people with psoriasis. Research into PsA pathogenesis has led to the development of targeted therapies, including Tumor Necrosis Factor inhibitors (TNF-i). Good response is only achieved by ~60% of patients leading to ‘trial and error’ drug management approaches, adverse reactions and increasing healthcare costs. Robust and well-validated biomarker identification, and subsequent development of sensitive and specific assays, would facilitate the implementation of a stratified approach into clinical care. This review will summarise potential genetic biomarkers for TNF-i (adalimumab, etanercept and infliximab) response that have been reported to date. It will also comment upon the importance of managing clinical confounders when understanding drug response prediction. Variants in multiple gene regions including TNF-A, FCGR2A, TNFAIP3, TNFR1/TNFR1A/TNFRSF1A, TRAIL-R1/TNFRSF10A, FCGR3A have been reported to correlate with TNF-i response at various levels of statistical significance in patients with PsA. However, results were often from heterogenous and underpowered cohorts and none are currently implemented into clinical practice. External validation of genetic biomarkers in large, well-documented cohorts is required, and assessment of the predictive value of combining multiple genetic biomarkers with clinical measures is essential to clinically embed pharmacogenomics into PsA drug management.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"23 1","pages":"1-7"},"PeriodicalIF":2.8,"publicationDate":"2022-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9925377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10849646","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: 4

Protein network and pathway analysis in a pharmacogenetic study of cyclosporine treatment response in Greek patients with psoriasis 希腊银屑病患者环孢素治疗反应药物遗传学研究中的蛋白质网络和通路分析

IF 2.8 3区医学

Pharmacogenomics Journal Pub Date : 2022-10-13 DOI: 10.1038/s41397-022-00291-7

Charalabos Antonatos, Aikaterini Patsatsi, Efterpi Zafiriou, Eleana F. Stavrou, Andreas Liaropoulos, Aikaterini Kyriakoy, Evangelos Evangelou, Danai Digka, Angeliki Roussaki-Schulze, Dimitris Sotiriadis, Sophia Georgiou, Katerina Grafanaki, Nicholas Κ. Moschonas, Yiannis Vasilopoulos

{"title":"Protein network and pathway analysis in a pharmacogenetic study of cyclosporine treatment response in Greek patients with psoriasis","authors":"Charalabos Antonatos, Aikaterini Patsatsi, Efterpi Zafiriou, Eleana F. Stavrou, Andreas Liaropoulos, Aikaterini Kyriakoy, Evangelos Evangelou, Danai Digka, Angeliki Roussaki-Schulze, Dimitris Sotiriadis, Sophia Georgiou, Katerina Grafanaki, Nicholas Κ. Moschonas, Yiannis Vasilopoulos","doi":"10.1038/s41397-022-00291-7","DOIUrl":"10.1038/s41397-022-00291-7","url":null,"abstract":"Although cyclosporine comprises a well-established systemic therapy for psoriasis, patients show important heterogeneity in their treatment response. The aim of our study was the pharmacogenetic analysis of 200 Greek patients with psoriasis based on the cyclosporine pathway related protein-protein interaction (PPI) network, reconstructed through the PICKLE meta-database. We genotyped 27 single nucleotide polymorphisms, mapped to 22 key protein nodes of the cyclosporine pathway, via the utilization of the iPLEX®GOLD panel of the MassARRAY® System. Single-SNP analyses showed statistically significant associations between CALM1 rs12885713 (P = 0.0108) and MALT1 rs2874116 (P = 0.0006) polymorphisms with positive response to cyclosporine therapy after correction for multiple comparisons, with the haplotype analyses further enhancing the predictive value of rs12885713 as a pharmacogenetic biomarker for cyclosporine therapy (P = 0.0173). Our findings have the potential to improve our prediction of cyclosporine efficacy and safety in psoriasis patients, as well as provide the framework for the pharmacogenetics of biological therapies in complex diseases.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"23 1","pages":"8-13"},"PeriodicalIF":2.8,"publicationDate":"2022-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10850066","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: 3

Drug genetic associations with COVID-19 manifestations: a data mining and network biology approach 药物基因与 COVID-19 表现的关联：一种数据挖掘和网络生物学方法

IF 2.8 3区医学

Pharmacogenomics Journal Pub Date : 2022-09-28 DOI: 10.1038/s41397-022-00289-1

Theodosia Charitou, Panagiota I. Kontou, Ioannis A. Tamposis, Georgios A. Pavlopoulos, Georgia G. Braliou, Pantelis G. Bagos

{"title":"Drug genetic associations with COVID-19 manifestations: a data mining and network biology approach","authors":"Theodosia Charitou, Panagiota I. Kontou, Ioannis A. Tamposis, Georgios A. Pavlopoulos, Georgia G. Braliou, Pantelis G. Bagos","doi":"10.1038/s41397-022-00289-1","DOIUrl":"10.1038/s41397-022-00289-1","url":null,"abstract":"Available drugs have been used as an urgent attempt through clinical trials to minimize severe cases of hospitalizations with Coronavirus disease (COVID-19), however, there are limited data on common pharmacogenomics affecting concomitant medications response in patients with comorbidities. To identify the genomic determinants that influence COVID-19 susceptibility, we use a computational, statistical, and network biology approach to analyze relationships of ineffective concomitant medication with an adverse effect on patients. We statistically construct a pharmacogenetic/biomarker network with significant drug-gene interactions originating from gene-disease associations. Investigation of the predicted pharmacogenes encompassing the gene-disease-gene pharmacogenomics (PGx) network suggests that these genes could play a significant role in COVID-19 clinical manifestation due to their association with autoimmune, metabolic, neurological, cardiovascular, and degenerative disorders, some of which have been reported to be crucial comorbidities in a COVID-19 patient.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"22 5-6","pages":"294-302"},"PeriodicalIF":2.8,"publicationDate":"2022-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9517961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40379690","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

Publisher Correction: Cyrius: accurate CYP2D6 genotyping using whole-genome sequencing data 出版商更正：Cyrius：利用全基因组测序数据准确进行CYP2D6基因分型

IF 2.8 3区医学

Pharmacogenomics Journal Pub Date : 2022-09-28 DOI: 10.1038/s41397-022-00287-3

Xiao Chen, Fei Shen, Nina Gonzaludo, Alka Malhotra, Cande Rogert, Ryan J. Taft, David R. Bentley, Michael A. Eberle

引用次数: 0

The genetic landscape of major drug metabolizing cytochrome P450 genes—an updated analysis of population-scale sequencing data 主要药物代谢细胞色素 P450 基因的遗传格局--对群体规模测序数据的最新分析

IF 2.8 3区医学

Pharmacogenomics Journal Pub Date : 2022-09-06 DOI: 10.1038/s41397-022-00288-2

Yitian Zhou, Volker M. Lauschke

{"title":"The genetic landscape of major drug metabolizing cytochrome P450 genes—an updated analysis of population-scale sequencing data","authors":"Yitian Zhou, Volker M. Lauschke","doi":"10.1038/s41397-022-00288-2","DOIUrl":"10.1038/s41397-022-00288-2","url":null,"abstract":"Genes encoding cytochrome P450 enzymes (CYPs) are extremely polymorphic and multiple CYP variants constitute clinically relevant biomarkers for the guidance of drug selection and dosing. We previously reported the distribution of the most relevant CYP alleles using population-scale sequencing data. Here, we update these findings by making use of the increasing wealth of data, incorporating whole exome and whole genome sequencing data from 141,614 unrelated individuals across 12 human populations. We furthermore extend our previous studies by systematically considering also uncharacterized rare alleles and reveal that they contribute between 1.5% and 17.5% to the overall genetically encoded functional variability. By using established guidelines, we aggregate and translate the available sequencing data into population-specific patterns of metabolizer phenotypes. Combined, the presented data refine the worldwide landscape of ethnogeographic variability in CYP genes and aspire to provide a relevant resource for the optimization of population-specific genotyping strategies and precision public health.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"22 5-6","pages":"284-293"},"PeriodicalIF":2.8,"publicationDate":"2022-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9674520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40354369","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: 15

Development of an extensive workflow for comprehensive clinical pharmacogenomic profiling: lessons from a pilot study on 100 whole exome sequencing data 为全面的临床药理基因组学分析开发广泛的工作流程：从 100 个全外显子组测序数据的试点研究中汲取的经验教训

IF 2.8 3区医学

Pharmacogenomics Journal Pub Date : 2022-08-13 DOI: 10.1038/s41397-022-00286-4

Alireza Tafazoli, Maaike van der Lee, Jesse J. Swen, Anna Zeller, Natalia Wawrusiewicz-Kurylonek, Hailiang Mei, Ruben H. P. Vorderman, Krzysztof Konopko, Andrzej Zankiewicz, Wojciech Miltyk

{"title":"Development of an extensive workflow for comprehensive clinical pharmacogenomic profiling: lessons from a pilot study on 100 whole exome sequencing data","authors":"Alireza Tafazoli, Maaike van der Lee, Jesse J. Swen, Anna Zeller, Natalia Wawrusiewicz-Kurylonek, Hailiang Mei, Ruben H. P. Vorderman, Krzysztof Konopko, Andrzej Zankiewicz, Wojciech Miltyk","doi":"10.1038/s41397-022-00286-4","DOIUrl":"10.1038/s41397-022-00286-4","url":null,"abstract":"This pilot study is aimed at implementing an approach for comprehensive clinical pharmacogenomics (PGx) profiling. Fifty patients with cardiovascular diseases and 50 healthy individuals underwent whole-exome sequencing. Data on 1800 PGx genes were extracted and analyzed through deep filtration separately. Theoretical drug induced phenoconversion was assessed for the patients, using sequence2script. In total, 4539 rare variants (including 115 damaging non-synonymous) were identified. Four publicly available PGx bioinformatics algorithms to assign PGx haplotypes were applied to nine selected very important pharmacogenes (VIP) and revealed a 45–70% concordance rate. To ensure availability of the results at point-of-care, actionable variants were stored in a web-hosted database and PGx-cards were developed for quick access and handed to the study subjects. While a comprehensive clinical PGx profile could be successfully extracted from WES data, available tools to interpret these data demonstrated inconsistencies that complicate clinical application.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"22 5-6","pages":"276-283"},"PeriodicalIF":2.8,"publicationDate":"2022-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9674517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40720493","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: 3

A blockchain-based framework to support pharmacogenetic data sharing 支持药物基因数据共享的区块链框架

IF 2.8 3区医学

Pharmacogenomics Journal Pub Date : 2022-07-22 DOI: 10.1038/s41397-022-00285-5

F. Albalwy, J. H. McDermott, W. G. Newman, A. Brass, A. Davies

{"title":"A blockchain-based framework to support pharmacogenetic data sharing","authors":"F. Albalwy, J. H. McDermott, W. G. Newman, A. Brass, A. Davies","doi":"10.1038/s41397-022-00285-5","DOIUrl":"10.1038/s41397-022-00285-5","url":null,"abstract":"The successful implementation of pharmacogenetics (PGx) into clinical practice requires patient genomic data to be shared between stakeholders in multiple settings. This creates a number of barriers to widespread adoption of PGx, including privacy concerns related to the storage and movement of identifiable genomic data. Informatic solutions that support secure and equitable data access for genomic data are therefore important to PGx. Here we propose a methodology that uses smart contracts implemented on a blockchain-based framework, PGxChain, to address this issue. The design requirements for PGxChain were identified through a systematic literature review, identifying technical challenges and barriers impeding the clinical implementation of pharmacogenomics. These requirements included security and privacy, accessibility, interoperability, traceability and legal compliance. A proof-of-concept implementation based on Ethereum was then developed that met the design requirements. PGxChain’s performance was examined using Hyperledger Caliper for latency, throughput, and transaction success rate. The findings clearly indicate that blockchain technology offers considerable potential to advance pharmacogenetic data sharing, particularly with regard to PGx data security and privacy, large-scale accessibility of PGx data, PGx data interoperability between multiple health care providers and compliance with data-sharing laws and regulations.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"22 5-6","pages":"264-275"},"PeriodicalIF":2.8,"publicationDate":"2022-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9674519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40639424","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: 3

The clinically relevant CYP2C8*3 and CYP2C9*2 haplotype is inherited from Neandertals 与临床相关的 CYP2C8*3 和 CYP2C9*2 单倍型是从尼安德特人那里遗传的

IF 2.8 3区医学

Pharmacogenomics Journal Pub Date : 2022-07-02 DOI: 10.1038/s41397-022-00284-6

Sigrid Haeggström, Magnus Ingelman-Sundberg, Svante Pääbo, Hugo Zeberg

引用次数: 2

A machine learning model using SNPs obtained from a genome-wide association study predicts the onset of vincristine-induced peripheral neuropathy 利用从全基因组关联研究中获得的 SNPs 的机器学习模型预测长春新碱诱发的周围神经病变的发病情况

IF 2.8 3区医学

Pharmacogenomics Journal Pub Date : 2022-06-25 DOI: 10.1038/s41397-022-00282-8

Hiroki Yamada, Rio Ohmori, Naoto Okada, Shingen Nakamura, Kumiko Kagawa, Shiro Fujii, Hirokazu Miki, Keisuke Ishizawa, Masahiro Abe, Youichi Sato

{"title":"A machine learning model using SNPs obtained from a genome-wide association study predicts the onset of vincristine-induced peripheral neuropathy","authors":"Hiroki Yamada, Rio Ohmori, Naoto Okada, Shingen Nakamura, Kumiko Kagawa, Shiro Fujii, Hirokazu Miki, Keisuke Ishizawa, Masahiro Abe, Youichi Sato","doi":"10.1038/s41397-022-00282-8","DOIUrl":"10.1038/s41397-022-00282-8","url":null,"abstract":"Vincristine treatment may cause peripheral neuropathy. In this study, we identified the genes associated with the development of peripheral neuropathy due to vincristine therapy using a genome-wide association study (GWAS) and constructed a predictive model for the development of peripheral neuropathy using genetic information-based machine learning. The study included 72 patients admitted to the Department of Hematology, Tokushima University Hospital, who received vincristine. Of these, 56 were genotyped using the Illumina Asian Screening Array-24 Kit, and a GWAS for the onset of peripheral neuropathy caused by vincristine was conducted. Using Sanger sequencing for 16 validation samples, the top three single nucleotide polymorphisms (SNPs) associated with the onset of peripheral neuropathy were determined. Machine learning was performed using the statistical software R package “caret”. The 56 GWAS and 16 validation samples were used as the training and test sets, respectively. Predictive models were constructed using random forest, support vector machine, naive Bayes, and neural network algorithms. According to the GWAS, rs2110179, rs7126100, and rs2076549 were associated with the development of peripheral neuropathy on vincristine administration. Machine learning was performed using these three SNPs to construct a prediction model. A high accuracy of 93.8% was obtained with the support vector machine and neural network using rs2110179 and rs2076549. Thus, peripheral neuropathy development due to vincristine therapy can be effectively predicted by a machine learning prediction model using SNPs associated with it.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"22 4","pages":"241-246"},"PeriodicalIF":2.8,"publicationDate":"2022-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40398491","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: 1