Browsing by Author "George P. Patrinos"

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    Discrepancies and similarities in the genome-informed guidance for psychiatric disorders amongst different regulatory bodies and research consortia using next generation sequencing-based clinical pharmacogenomics data
    (2021-05-01) Zoe Kordou; Maria Skokou; Evangelia Eirini Tsermpini; Wasun Chantratita; Koya Fukunaga; Taisei Mushiroda; George P. Patrinos; Maria Koromina; College of Medicine and Health Sciences United Arab Emirates University; School of Health Sciences; General Hospital Agios Andreas; Riken; Faculty of Medicine Ramathibodi Hospital, Mahidol University; United Arab Emirates University; The Golden Helix Foundation
    Undoubtedly, pharmacogenomics (PGx) aims in optimizing drug treatment responses whilst also improving the patients’ quality of life, either via a reduction of adverse drug reactions and/or an enhancement of drug treatment efficacy. To achieve this, PGx guidance is provided by the two major regulatory bodies in a worldwide level, specifically the U.S. Food and Drug Administration (FDA) and the European Medicine Agency (EMA), and occasionally some research consortia, such as the Clinical Pharmacogenetics Implementation Consortium (CPIC) or the Dutch Pharmacogenomics Working Group (DPWG). However, so far, there is a limited number of studies focusing on the delineation of the similarities and more importantly, the discrepancies in the PGx guidance by the different regulatory bodies and consortia. Herein, we use real-life clinical PGx data to highlight such discrepancies and similarities for genome-guided interventions in psychiatric disorders, thus demonstrating the need for harmonization of the guidelines and recommendations. More precisely, we used the PharmCAT genome-informed drug treatment reports from 304 Greek individuals with psychiatric disorders in order to emphasize on the discrepancies in the PGx guidance/guidelines between FDA vs EMA and CPIC vs DPWG, respectively. For example, CYP2D6-pimozide pair is characterized as ‘Testing Required’ according to FDA and is accompanied by a DPWG PGx guideline, whilst no EMA or CPIC PGx guidance is found for this drug-gene pair. Moreover, discrepancies are observed regarding the type of PGx guidance for CYP2C19-doxepin pair, with 89 individuals from our study cohort requiring a dose prescribing change based on FDA, whilst only 5 individuals have to receive genome-guided treatment adjustment according to CPIC. To our knowledge, this is the first study, in which discrepancies regarding the type of PGx guidance and the number of actionable drug-gene pairs amongst FDA and EMA, as well as CPIC and DPWG, are brought to light with an emphasis on psychiatric disorders.
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    Drug-induced stevens-johnson syndrome and toxic epidermal necrolysis call for optimum patient stratification and theranostics via pharmacogenomics
    (2018-08-31) Chonlaphat Sukasem; Theodora Katsila; Therdpong Tempark; George P. Patrinos; Wasun Chantratita; College of Medicine and Health Sciences United Arab Emirates University; Panepistimion Patron; Chulalongkorn University; Faculty of Medicine, Ramathibodi Hospital, Mahidol University
    Copyright © 2018 by Annual Reviews. All rights reserved. The Global Genomic Medicine Collaborative, a multinational coalition of genomic and policy experts working to implement genomics in clinical care, considers pharmacogenomics to be among the first areas in genomic medicine that can provide guidance in routine clinical practice, by linking genetic variation and drug response. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe life-threatening reactions to medications with a high incidence worldwide. Genomic screening prior to drug administration is a key opportunity and potential paradigm for using genomic medicine to reduce morbidity and mortality and ultimately eliminate one of the most devastating adverse drug reactions. This review focuses on the current understanding of the surveillance, pathogenesis, and treatment of SJS/TEN, including the role of genomics and pharmacogenomics in the etiology, treatment, and eradication of preventable causes of drug-induced SJS/TEN. Gaps, unmet needs, and priorities for future research have been identified for the optimal management of drug-induced SJS/TEN in various ethnic populations. Pharmacogenomics holds great promise for optimal patient stratification and theranostics, yet its clinical implementation needs to be cost-effective and sustainable.
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    Genomic Medicine in Developing Countries and Resource-Limited Environments
    (2016-11-25) T. Katsila; K. Mitropoulos; Z. Mohamed; D. A. Forero; P. Laissue; A. Wonkam; C. Lopez-Correa; W. Chantratita; A. Llerena; B. R. Ali; George P. Patrinos; University of Patras School of Health Sciences; The Golden Helix Foundation; University of Malaya; Universidad Antonio Nariño; Universidad del Rosario; University of Cape Town; Genome Quebec; Mahidol University; Universidad de Extremadura; United Arab Emirates University; Erasmus University Medical Center
    © 2017 Elsevier Ltd. All rights reserved. Even though the translation of genomic discoveries into clinic and public health has gained momentum, major discrepancies still occur between developed and developing/resource-limited countries. Genomic medicine is implemented at a different pace not only due to limited resources but also because of the slow pace toward the adoption of new findings. The potential of genomic medicine to rationalize medical diagnosis and treatment has been poorly understood. In this chapter, we discuss examples from the successful implementation of genomic medicine in developing countries. We feel that these examples can serve as model cases toward the implementation of genomic medicine in resource-limited environments.
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    Genomic Medicine Without Borders: Which Strategies Should Developing Countries Employ to Invest in Precision Medicine? A New Fast-Second Winner Strategy
    (2017-11-01) Konstantinos Mitropoulos; David N. Cooper; Christina Mitropoulou; Spiros Agathos; Jürgen K.V. Reichardt; Fatima Al-Maskari; Wasun Chantratita; Ambroise Wonkam; Collet Dandara; Theodora Katsila; Catalina Lopez-Correa; Bassam R. Ali; George P. Patrinos; University of Athens; Cardiff University; The Golden Helix Foundation; Yachay Tech; College of Medicine and Health Sciences United Arab Emirates University; United Arab Emirates University; Mahidol University; University of Cape Town; Panepistimion Patron; Genome British Columbia
    © 2017, Mary Ann Liebert, Inc. Genomic medicine has greatly matured in terms of its technical capabilities, but the diffusion of genomic innovations worldwide faces significant barriers beyond mere access to technology. New global development strategies are sorely needed for biotechnologies such as genomics and their applications toward precision medicine without borders. Moreover, diffusion of genomic medicine globally cannot adhere to a "one-size-fits-all-countries" development strategy, in the same way that drug treatments should be customized. This begs a timely, difficult but crucial question: How should developing countries, and the resource-limited regions of developed countries, invest in genomic medicine? Although a full-scale investment in infrastructure from discovery to the translational implementation of genomic science is ideal, this may not always be feasible in all countries at all times. A simple "transplantation of genomics" from developed to developing countries is unlikely to be feasible. Nor should developing countries be seen as simple recipients and beneficiaries of genomic medicine developed elsewhere because important advances in genomic medicine have materialized in developing countries as well. There are several noteworthy examples of genomic medicine success stories involving resource-limited settings that are contextualized and described in this global genomic medicine innovation analysis. In addition, we outline here a new long-term development strategy for global genomic medicine in a way that recognizes the individual country's pressing public health priorities and disease burdens. We term this approach the "Fast-Second Winner" model of innovation that supports innovation commencing not only "upstream" of discovery science but also "mid-stream," building on emerging highly promising biomarker and diagnostic candidates from the global science discovery pipeline, based on the unique needs of each country. A mid-stream entry into innovation can enhance collective learning from other innovators' mistakes upstream in discovery science and boost the probability of success for translation and implementation when resources are limited. This à la carte model of global innovation and development strategy offers multiple entry points into the global genomics innovation ecosystem for developing countries, whether or not extensive and expensive discovery infrastructures are already in place. Ultimately, broadening our thinking beyond the linear model of innovation will help us to enable the vision and practice of genomics without borders in both developed and resource-limited settings.
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    Global implementation of genomic medicine: We are not alone
    (2015-06-03) Teri A. Manolio; Marc Abramowicz; Fahd Al-Mulla; Warwick Anderson; Rudi Balling; Adam C. Berger; Steven Bleyl; Aravinda Chakravarti; Wasun Chantratita; Rex L. Chisholm; Vajira H.W. Dissanayake; Michael Dunn; Victor J. Dzau; Bok Ghee Han; Tim Hubbard; Anne Kolbe; Bruce Korf; Michiaki Kubo; Paul Lasko; Erkki Leego; Surakameth Mahasirimongkol; Partha P. Majumdar; Gert Matthijs; Howard L. McLeod; Andres Metspalu; Pierre Meulien; Satoru Miyano; Yaakov Naparstek; P. Pearl O'Rourke; George P. Patrinos; Heidi L. Rehm; Mary V. Relling; Gad Rennert; Laura Lyman Rodriguez; Dan M. Roden; Alan R. Shuldiner; Sukdeb Sinha; Patrick Tan; Mats Ulfendahl; Robyn Ward; Marc S. Williams; John E.L. Wong; Eric D. Green; Geofrey S. Ginsburg; National Human Genome Research Institute; Université libre de Bruxelles (ULB); University of Kuwait; Australian Government; University of Luxembourg; Institute of Medicine - Washington; Intermountain Healthcare; The Johns Hopkins School of Medicine; Mahidol University; Northwestern University Feinberg School of Medicine; University of Colombo Faculty of Medicine; Wellcome Trust; National Academy of Medicine; Korea National Institute of Health; King's College London; National Health Committee; University of Alabama at Birmingham; Riken; McGill University; University of Tartu; Thailand Ministry of Public Health; Indian Statistical Institute, Kolkata; KU Leuven; Moffitt Cancer Center; Genome Canada; Institute of Medical Science The University of Tokyo; Hadassah University Medical Centre; Partners HealthCare; Panepistimion Patron; St. Jude Children's Research Hospital; Carmel Medical Center; Vanderbilt University School of Medicine; University of Maryland School of Medicine; Ministry of Science And Technology, India; Duke-NUS Medical School Singapore; Swedish Research Council; University of Queensland; Geisinger Health System; National University of Singapore; Duke University; Genomics England
    © 2015, American Association for the Advancement of Science. All rights reserved. Around the world, innovative genomic-medicine programs capitalize on singular capabilities arising from local health care systems, cultural or political milieus, and unusual selected risk alleles or disease burdens. Such individual eforts might beneft from the sharing of approaches and lessons learned in other locales. The U.S. National Human Genome Research Institute and the National Academy of Medicine recently brought together 25 of these groups to compare projects, to examine the current state of implementation and desired near-term capabilities, and to identify opportunities for collaboration that promote the responsible practice of genomic medicine. Eforts to coalesce these groups around concrete but compelling signature projects should accelerate the responsible implementation of genomic medicine in eforts to improve clinical care worldwide.
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    Pharmacogenomics variants are associated with BMI differences between individuals with bipolar and other psychiatric disorders
    (2021-08-01) Aggeliki Charalampidi; Zoe Kordou; Evangelia Eirini Tsermpini; Panagiotis Bosganas; Wasun Chantratita; Koya Fukunaga; Taisei Mushiroda; George P. Patrinos; Maria Koromina; Ramathibodi Hospital; College of Medicine and Health Sciences United Arab Emirates University; School of Health Sciences; Riken; United Arab Emirates University; The Golden Helix Foundation
    Aim: Regardless of the plethora of next-generation sequencing studies in the field of pharmacogenomics (PGx), the potential effect of covariate variables on PGx response within deeply phenotyped cohorts remains unexplored. Materials & methods: We explored with advanced statistical methods the potential influence of BMI, as a covariate variable, on PGx response in a Greek cohort with psychiatric disorders. Results: Nine PGx variants within UGT1A6, SLC22A4, GSTP1, CYP4B1, CES1, SLC29A3 and DPYD were associated with altered BMI in different psychiatric disorder groups. Carriers of rs2070959 (UGT1A6), rs199861210 (SLC29A3) and rs2297595 (DPYD) were also characterized by significant changes in the mean BMI, depending on the presence of psychiatric disorders. Conclusion: Specific PGx variants are significantly associated with BMI in a Greek cohort with psychiatric disorders.
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    Prevalence of pharmacogenomic variants in 100 pharmacogenes among Southeast Asian populations under the collaboration of the Southeast Asian Pharmacogenomics Research Network (SEAPharm)
    (2021-12-01) Chakkaphan Runcharoen; Koya Fukunaga; Insee Sensorn; Nareenart Iemwimangsa; Sommon Klumsathian; Hang Tong; Nam Sy Vo; Ly Le; Tin Maung Hlaing; Myo Thant; Shamsul Mohd Zain; Zahurin Mohamed; Yuh Fen Pung; Francis Capule; Jose Nevado; Catherine Lynn Silao; Zeina N. Al-Mahayri; Bassam R. Ali; Rika Yuliwulandari; Kinasih Prayuni; Hilyatuz Zahroh; Dzul Azri Mohamed Noor; Phonepadith Xangsayarath; Dalouny Xayavong; Sengchanh Kounnavong; Somphou Sayasone; Zoe Kordou; Ioannis Liopetas; Athina Tsikrika; Evangelia Eirini Tsermpini; Maria Koromina; Christina Mitropoulou; George P. Patrinos; Aumpika Kesornsit; Angkana Charoenyingwattana; Sukanya Wattanapokayakit; Surakameth Mahasirimongkol; Taisei Mushiroda; Wasun Chantratita; Faculty of Medicine, YARSI University; YARSI University; School of Pharmaceutical Sciences, Universiti Sains Malaysia; International University,Vietnam National University Ho Chi Minh City; The University of Nottingham Malaysia Campus; University of the Philippines Manila; University of the Philippines College of Medicine; College of Medicine and Health Sciences United Arab Emirates University; School of Health Sciences; Universiti Malaya; Riken; Faculty of Medicine Ramathibodi Hospital, Mahidol University; Thailand Ministry of Public Health; Mahidol University; Defence Services Medical Research Centre; Defence Services Medical Academy; Vingroup Big Data Institute; Lao Tropical and Public Health Institute; The Golden Helix Foundation; National Center for Laboratory and Epidemiology
    Pharmacogenomics can enhance the outcome of treatment by adopting pharmacogenomic testing to maximize drug efficacy and lower the risk of serious adverse events. Next-generation sequencing (NGS) is a cost-effective technology for genotyping several pharmacogenomic loci at once, thereby increasing publicly available data. A panel of 100 pharmacogenes among Southeast Asian (SEA) populations was resequenced using the NGS platform under the collaboration of the Southeast Asian Pharmacogenomics Research Network (SEAPharm). Here, we present the frequencies of pharmacogenomic variants and the comparison of these pharmacogenomic variants among different SEA populations and other populations used as controls. We investigated the different types of pharmacogenomic variants, especially those that may have a functional impact. Our results provide substantial genetic variations at 100 pharmacogenomic loci among SEA populations that may contribute to interpopulation variability in drug response phenotypes. Correspondingly, this study provides basic information for further pharmacogenomic investigations in SEA populations.
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    Success stories in genomic medicine from resource-limited countries
    (2015-01-01) Konstantinos Mitropoulos; Hayat Al Jaibeji; Diego A. Forero; Paul Laissue; Ambroise Wonkam; Catalina Lopez-Correa; Zahurin Mohamed; Wasun Chantratita; Ming Ta Michael Lee; Adrian Llerena; Angela Brand; Bassam R. Ali; George P. Patrinos; The Golden Helix Foundation; Maastricht University; College of Medicine and Health Sciences United Arab Emirates University; Universidad Antonio Nariño; Universidad del Rosario; University of Cape Town, Faculty of Health Sciences; Genome Quebec; University of Malaya; Mahidol University; Riken; Academia Sinica, Institute of Biomedical Sciences; Universidad de Extremadura; Panepistimion Patron
    © 2015 Mitropoulos et al. In recent years, the translation of genomic discoveries into mainstream medical practice and public health has gained momentum, facilitated by the advent of new technologies. However, there are often major discrepancies in the pace of implementation of genomic medicine between developed and developing/resource-limited countries. The main reason does not only lie in the limitation of resources but also in the slow pace of adoption of the new findings and the poor understanding of the potential that this new discipline offers to rationalize medical diagnosis and treatment. Here, we present and critically discuss examples from the successful implementation of genomic medicine in resource-limited countries, focusing on pharmacogenomics, genome informatics, and public health genomics, emphasizing in the latter case genomic education, stakeholder analysis, and economics in pharmacogenomics. These examples can be considered as model cases and be readily replicated for the wide implementation of pharmacogenomics and genomic medicine in other resource-limited environments.