PharmacogenomicsPub Date : 2023-08-01Epub Date: 2023-09-14DOI: 10.2217/pgs-2023-0111
Ronaldo Elkaddoum, John Zakhour, Mary Hajal, Maroun Aoun, Maria Njeim, Mirvat Mahrous, Humaid O Al-Shamsi, Zineb Ben Brahim, Sami A Khatib, Hampig Raphael Kourie
{"title":"Improving the management of ALK-rearranged non-small-cell lung cancer through a mobile application: a physicians-based survey.","authors":"Ronaldo Elkaddoum, John Zakhour, Mary Hajal, Maroun Aoun, Maria Njeim, Mirvat Mahrous, Humaid O Al-Shamsi, Zineb Ben Brahim, Sami A Khatib, Hampig Raphael Kourie","doi":"10.2217/pgs-2023-0111","DOIUrl":"10.2217/pgs-2023-0111","url":null,"abstract":"<p><p><b>Background:</b> ALK rearrangements account for around 5% of non-small-cell lung cancers. <b>Aim:</b> This study surveys physicians on the potential efficacy of a mobile application in improving the management of ALK-rearranged non-small-cell lung cancer, through knowledge, treatment adherence and real-time adverse events reporting. <b>Materials & methods:</b> A total of 118 physicians from 11 countries in the Middle East participated. <b>Results & conclusion:</b> Results indicate 94% support for enhancing team communication via an application, and 93% believe real-time adverse events reporting improves the quality of care. Participants found an ALK-rearrangement patient-physicians forum valuable for communication improvement. Motivations for application use included treatment planning (73%), care enhancement (60%) and contributing to publications (40%).</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"725-730"},"PeriodicalIF":2.1,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10286717","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}
PharmacogenomicsPub Date : 2023-07-01Epub Date: 2023-07-19DOI: 10.2217/pgs-2023-0119
Kristen Suhrie, Emma M Tillman
{"title":"Pharmacogenetic informed care in early childhood: options for improving access and health equity.","authors":"Kristen Suhrie, Emma M Tillman","doi":"10.2217/pgs-2023-0119","DOIUrl":"10.2217/pgs-2023-0119","url":null,"abstract":"","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":"24 11","pages":"579-582"},"PeriodicalIF":2.1,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10228350","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}
PharmacogenomicsPub Date : 2023-07-01Epub Date: 2023-07-12DOI: 10.2217/pgs-2023-0089
Marie Madeleine M Hidjo, Zedias Chikwambi, Gift Ngwende, Jonathan A Matenga, Collen Masimirembwa
{"title":"Warfarin pharmacogenetics in a black Zimbabwean cohort: an observational prospective study.","authors":"Marie Madeleine M Hidjo, Zedias Chikwambi, Gift Ngwende, Jonathan A Matenga, Collen Masimirembwa","doi":"10.2217/pgs-2023-0089","DOIUrl":"10.2217/pgs-2023-0089","url":null,"abstract":"<p><p><b>Aim:</b> A prospective observational study was conducted to evaluate the feasibility of implementing clinical guidelines for warfarin dosing in black Zimbabwean patients. <b>Methods:</b> <i>CYP2C9*5</i>, <i>CYP2C9*6</i>, <i>CYP2C9*8</i> and <i>CYP2C9*11</i> and <i>VKORC1</i> c. 1639 G>A variations were observed in 62 study patients. <b>Results & Conclusion:</b> Overall, 39/62 (62.90%) participants did not receive a warfarin starting dose as would have been recommended by Clinical Pharmacogenetics Implementation Consortium guidelines. US FDA and Dutch Pharmacogenetics Working Group guidelines are based on <i>CYP2C9*2</i> and <i>CYP2C9*3</i> only, hence, unlikely useful in this cohort, where such variants were not detected. Clinical Pharmacogenetics Implementation Consortium guidelines, on the other hand, have a specific recommendation on the African-specific variants <i>CYP2C9*5</i>, <i>CYP2C9*6</i> and <i>CYP2C9*11</i>, and are hence suitable for implementation in Zimbabwe and would help optimize warfarin doses in patients in the study cohort.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":"24 10","pages":"529-538"},"PeriodicalIF":1.9,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10621760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10037089","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}
PharmacogenomicsPub Date : 2023-07-01Epub Date: 2023-08-08DOI: 10.2217/pgs-2023-0091
Estee Y Cramer, Jacquelaine Bartlett, Ernest R Chan, Andrea Gaedigk, Arsene C Ratsimbasoa, Rajeev K Mehlotra, Scott M Williams, Peter A Zimmerman
{"title":"Pharmacogenomic variation in the Malagasy population: implications for the antimalarial drug primaquine metabolism.","authors":"Estee Y Cramer, Jacquelaine Bartlett, Ernest R Chan, Andrea Gaedigk, Arsene C Ratsimbasoa, Rajeev K Mehlotra, Scott M Williams, Peter A Zimmerman","doi":"10.2217/pgs-2023-0091","DOIUrl":"10.2217/pgs-2023-0091","url":null,"abstract":"<p><p><b>Aim:</b> Antimalarial primaquine (PQ) eliminates liver hypnozoites of <i>Plasmodium vivax.</i> <i>CYP2D6</i> gene variation contributes to PQ therapeutic failure. Additional gene variation may contribute to PQ efficacy. Information on pharmacogenomic variation in Madagascar, with <i>vivax</i> malaria and a unique population admixture, is scanty. <b>Methods:</b> The authors performed genome-wide genotyping of 55 Malagasy samples and analyzed data with a focus on a set of 28 pharmacogenes most relevant to PQ. <b>Results:</b> Mainly, the study identified 110 coding or splicing variants, including those that, based on previous studies in other populations, may be implicated in PQ response and copy number variation, specifically in chromosomal regions that contain pharmacogenes. <b>Conclusion:</b> With this pilot information, larger genome-wide association analyses with PQ metabolism and response are substantially more feasible.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":"24 11","pages":"583-597"},"PeriodicalIF":1.9,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10621762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10235989","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}
PharmacogenomicsPub Date : 2023-07-01Epub Date: 2023-07-28DOI: 10.2217/pgs-2023-0068
Nhlamulo Khoza, David Twesigomwe, Houcemeddine Othman
{"title":"Characterizing the combined effects of cytochrome P450 missense variation within star allele definitions.","authors":"Nhlamulo Khoza, David Twesigomwe, Houcemeddine Othman","doi":"10.2217/pgs-2023-0068","DOIUrl":"10.2217/pgs-2023-0068","url":null,"abstract":"<p><p><b>Background:</b> Cytochrome P450 (CYP) genetic variation largely impacts drug response. However, many CYP star alleles (haplotypes) lack functional annotation, impeding our understanding of drug metabolism mechanisms. We aimed to investigate the impact of missense variant combinations on CYP protein structures. <b>Methods:</b> Normal mode analysis was conducted on 261 missense variants within 91 CYP haplotypes. <i>CYP2D6*2</i> and <i>CYP2D6*17</i> were prioritized for molecular dynamics simulation. <b>Results:</b> Normal mode analysis and molecular dynamics highlight the effects of known CYP missense variants on protein stability and conformational dynamics. Missense variants within haplotypes may have intermodulating effects on protein structure and function. <b>Conclusion:</b> This study highlights the utility of multiscale modeling in interpreting CYP missense variants and particularly their combinations within various star alleles.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":"24 10","pages":"561-578"},"PeriodicalIF":2.1,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10038488","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}
{"title":"Association of <i>IL4RA</i> polymorphism in predicting susceptibility toward chronic obstructive pulmonary disease.","authors":"Depanshi Pandit, Parul Sharma, Harsh Yadav, Kranti Garg, Vishal Chopra, Siddharth Sharma","doi":"10.2217/pgs-2023-0010","DOIUrl":"10.2217/pgs-2023-0010","url":null,"abstract":"<p><p><b>Background:</b> The cytokine IL-4 plays vital role in the intercellular signalling network during immune responses to allergen exposure. <b>Methods:</b> This cross-sectional study involved 202 chronic obstructive pulmonary disease (COPD) patients and 203 healthy individuals. The genotyping of <i>IL4RAQ576R</i> gene polymorphism was determined using PCR restriction fragment length polymorphism analysis. <b>Results:</b> Significant association between mutant genotype (GG) and combined (AA+AG) genotype for the risk of COPD was found (odds ratio [OR]: 4.32; p = 0.04). A significant protective effect was observed between the <i>IL4RAQ576R</i> polymorphism and Global Strategy for Obstructive Lung Disease (GOLD) stage four patients in a recessive model (AA+AG vs GG; p = 0.002). In GOLD A, a substantial relationship was found between the AG and wild-type genotypes (AA) for COPD risk (OR: 2.38; p = 0.03). A strong association was found for COPD duration of 5-10 years (OR: 8.80; p = 0.01). <b>Conclusion:</b> <i>IL4RAQ576R</i> polymorphism is associated with COPD susceptibility.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":"24 11","pages":"615-627"},"PeriodicalIF":2.1,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10334315","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}
PharmacogenomicsPub Date : 2023-07-01Epub Date: 2023-07-28DOI: 10.2217/pgs-2023-0058
Nomusa M Zondo, Parveen Sobia, Aida Sivro, Sinaye Ngcapu, Leila E Mansoor, Sharana Mahomed, Lara Lewis, Veron Ramsuran, Derseree Archary
{"title":"Single-nucleotide polymorphisms in ABC drug transporters alter expression and circulating tenofovir in healthy South African women exposed to pre-exposure prophylaxis.","authors":"Nomusa M Zondo, Parveen Sobia, Aida Sivro, Sinaye Ngcapu, Leila E Mansoor, Sharana Mahomed, Lara Lewis, Veron Ramsuran, Derseree Archary","doi":"10.2217/pgs-2023-0058","DOIUrl":"10.2217/pgs-2023-0058","url":null,"abstract":"<p><p><b>Aim:</b> We investigated if single-nucleotide polymorphisms (SNPs) in ATP-binding cassette (ABC) drug transporters alter gene expression and tenofovir disposition in South African women taking Truvada<sup>®</sup> for HIV prevention. <b>Materials & methods:</b> In 393 women, real-time PCR was used to determine the associations between six SNPs in ABC transporter genes, mRNA expression and circulating-tenofovir. <b>Results:</b> Univariable and multivariable analyses showed that CT and TT relative to CC genotypes for the <i>ABCC4</i>(3463C/T) SNP had significantly higher tenofovir levels. In contrast, the AA genotype for the <i>ABCC4</i>(4976A/G) SNP showed significantly less tenofovir, while mRNA expression was increased. <b>Conclusion:</b> SNPs in the <i>ABCC4</i> gene may differentially affect gene expression and circulating tenofovir. Their impact may inform on low pre-exposure prophylaxis efficacy and discern effective drugs in clinical trials of African women enriched for certain genotypes.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":"24 11","pages":"599-613"},"PeriodicalIF":2.1,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10585626","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}
{"title":"<i>PMAT</i> variant rs3889348 is associated with metformin-induced gastrointestinal among Chinese Type 2 diabetes patients.","authors":"Ziqing Liu, Xiao Jia, Peng Wu, Benrui Wu, Ying Pan, Shao Zhong, Luhua Xiao, Yuehong Song, Jinbo Hu, Kaixin Zhou","doi":"10.2217/pgs-2023-0078","DOIUrl":"10.2217/pgs-2023-0078","url":null,"abstract":"<p><p><b>Aim:</b> This study examined intronic gene variants for their association with metformin intolerance in a Chinese population, focusing on the plasma monoamine transporter (<i>PMAT</i>) cis-protein expression quantitative trait loci (cis-eQTL) variant rs3889348. <b>Methods:</b> We recruited Type 2 diabetes patients from two hospitals and identified 111 metformin-intolerant patients using a questionnaire, and selected 206 metformin-tolerant patients from 2180 Type 2 diabetes mellitus patients. Genetic testing revealed an association between adverse gastrointestinal (GI) effects and <i>SLC22A1</i> and <i>PMAT</i>. <b>Results:</b> The single-nucleotide polymorphism rs3889348 is associated with metformin-induced adverse GI effects. Each additional copy of the G allele increases the score by 5.23 (95% CI: 1.82-8.64; p = 0.003). Patients taking more transporter inhibitors were more likely to respond to metformin-induced GI intolerance (p = 0.042). <b>Conclusion:</b> <i>PMAT</i> cis-eQTL rs3889348 was significantly associated with metformin-induced adverse GI effects.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":"24 10","pages":"551-560"},"PeriodicalIF":2.1,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10177991","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}
PharmacogenomicsPub Date : 2023-07-01Epub Date: 2023-08-08DOI: 10.2217/pgs-2022-0147
D Maroeska Wm Te Loo, Veroniek Harbers, Lars Vermeltfoort, Marieke Jh Coenen
{"title":"Influence of genetic variants on the pharmacokinetics and pharmacodynamics of sirolimus: a systematic review.","authors":"D Maroeska Wm Te Loo, Veroniek Harbers, Lars Vermeltfoort, Marieke Jh Coenen","doi":"10.2217/pgs-2022-0147","DOIUrl":"10.2217/pgs-2022-0147","url":null,"abstract":"<p><p>Sirolimus is an antiproliferative and immunosuppressive compound inhibiting the mTOR pathway, which is often activated in congenital low-flow vascular malformations. Studies have demonstrated the efficacy of sirolimus for this disease. Studies in kidney transplant patients suggest that genetic variants can influence these pharmacokinetic parameters. Therefore, a systematic literature search was performed to gain insight into pharmacogenetic studies with sirolimus. Most studies investigated <i>CYP3A4</i> and <i>CYP3A5</i>, with inconsistent results. No pharmacogenetic studies focusing on sirolimus have been performed for low-flow vascular malformations. We analyzed two common variants of <i>CYP3A4</i> and <i>CYP3A5</i> (<i>CYP3A4*22</i> and <i>CYP3A5*3</i>, respectively) in patients (n = 59) with congenital low-flow vascular malformations treated with sirolimus. No association with treatment outcome was identified in this small cohort of patients.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":"24 11","pages":"629-639"},"PeriodicalIF":2.1,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10235988","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}
PharmacogenomicsPub Date : 2023-07-01Epub Date: 2023-07-17DOI: 10.2217/pgs-2023-0112
Mirko Manchia, Martino Belvederi Murri
{"title":"The role of pharmacogenomics in precision psychiatry.","authors":"Mirko Manchia, Martino Belvederi Murri","doi":"10.2217/pgs-2023-0112","DOIUrl":"10.2217/pgs-2023-0112","url":null,"abstract":"<p><p>The field of psychiatry is facing an important paradigm shift in the provision of clinical care and mental health service organization toward personalization and integration of multimodal data science. This approach, termed precision psychiatry, aims at identifying subgroups of patients more prone to the development of a certain phenotype, such as symptoms or severe mental disorders (risk detection), and/or to guide treatment selection. Pharmacogenomics and computational psychiatry are two fundamental tools of precision psychiatry, which have seen increasing levels of integration in clinical settings. Here we present a brief overview of these two applications of precision psychiatry in clinical settings.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":"24 10","pages":"523-527"},"PeriodicalIF":2.1,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10042544","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}