دورية أكاديمية
Genomics, epigenomics and pharmacogenomics of familial hypercholesterolemia (FHBGEP): A study protocol.
| العنوان: | Genomics, epigenomics and pharmacogenomics of familial hypercholesterolemia (FHBGEP): A study protocol. |
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| المؤلفون: | Borges JB; School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil; Institute Dante Pazzanese of Cardiology, Sao Paulo, Brazil. Electronic address: jessica.bassani.borges@gmail.com., Oliveira VF; School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil. Electronic address: fo.victor@hotmail.com., Ferreira GM; School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil; Institute Dante Pazzanese of Cardiology, Sao Paulo, Brazil. Electronic address: glauciom.ferreira@gmail.com., Los B; School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil. Electronic address: brunalos17@gmail.com., Barbosa TKAA; School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil. Electronic address: thais.almendros@gmail.com., Marçal EDSR; School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil. Electronic address: elisangela.idpc@gmail.com., Dagli-Hernandez C; School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil. Electronic address: carolina.dagli@gmail.com., de Freitas RCC; School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil. Electronic address: renata_karoline@hotmail.com., Bortolin RH; School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil. Electronic address: raulhbortolin@yahoo.com.br., Mori AA; School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil. Electronic address: augusto.akira.mori@usp.br., Hirata TDC; School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil. Electronic address: thiagodch@gmail.com., Nakaya HTI; School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil. Electronic address: hnakaya@usp.br., Bastos GM; Institute Dante Pazzanese of Cardiology, Sao Paulo, Brazil; Real e Benemerita Associação Portuguesa de Beneficiência, Sao Paulo, Brazil. Electronic address: gimebastos@gmail.com., Thurow HS; School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil. Electronic address: thurow.hs@gmail.com., Gonçalves RM; Institute Dante Pazzanese of Cardiology, Sao Paulo, Brazil. Electronic address: rodrigomg@gmail.com., Araujo DB; Institute Dante Pazzanese of Cardiology, Sao Paulo, Brazil. Electronic address: dbaraujo@gmail.com., Zatz HP; Institute Dante Pazzanese of Cardiology, Sao Paulo, Brazil. Electronic address: hpzatz@gmail.com., Bertolami A; Institute Dante Pazzanese of Cardiology, Sao Paulo, Brazil. Electronic address: adriana@cardiologiabertolami.com., Faludi AA; Institute Dante Pazzanese of Cardiology, Sao Paulo, Brazil. Electronic address: aaf.2312@gmail.com., Bertolami MC; Institute Dante Pazzanese of Cardiology, Sao Paulo, Brazil. Electronic address: bertolami@uol.com.br., Sousa AGMR; Institute Dante Pazzanese of Cardiology, Sao Paulo, Brazil. Electronic address: amandars@cardiol.br., França JÍD; Institute Dante Pazzanese of Cardiology, Sao Paulo, Brazil. Electronic address: jitalo@lee.dante.br., Jannes CE; Heart Institute, University of Sao Paulo, Sao Paulo, Brazil. Electronic address: cejannes@hotmail.com., Pereira ADC; Heart Institute, University of Sao Paulo, Sao Paulo, Brazil. Electronic address: acplbmpereira@gmail.com., Nakazone MA; Sao Jose do Rio Preto Medical School, Sao Jose do Rio Preto, Brazil. Electronic address: naka_med@yahoo.com., Souza DRS; Sao Jose do Rio Preto Medical School, Sao Jose do Rio Preto, Brazil. Electronic address: doroteiasouza@yahoo.com., Carmo TS; Sao Jose do Rio Preto Medical School, Sao Jose do Rio Preto, Brazil. Electronic address: tay.scarmo@gmail.com., Sampaio MF; Real e Benemerita Associação Portuguesa de Beneficiência, Sao Paulo, Brazil. Electronic address: msampaio@cardiol.br., Gorjão R; Cruzeiro do Sul University, Sao Paulo, Brazil. Electronic address: renata.gorjao@cruzeirodosul.edu.br., Pithon-Curi TC; Cruzeiro do Sul University, Sao Paulo, Brazil. Electronic address: tania.pithon-curi@cruzeirodosul.edu.br., Moriel P; Faculty of Pharmaceutical Sciences, University of Campinas, Campinas, Brazil. Electronic address: morielpatricia@gmail.com., Silbiger VN; Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Brazil. Electronic address: viviansilbiger@hotmail.com., Luchessi AD; Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Brazil. Electronic address: andre.luchessi@outlook.com., de Araújo JNG; Northeast Biotechnology Network (RENORBIO), Graduate Program in Biotechnology, Federal University of Rio Grande do Norte, Natal, Brazil. Electronic address: jessnaysub@hotmail.com., Naslavsky MS; Human Genome and Stem-Cell Research Center, Biosciences Institute, University of Sao Paulo, Sao Paulo, Brazil. Electronic address: mnaslavsky@gmail.com., Wang JYT; Human Genome and Stem-Cell Research Center, Biosciences Institute, University of Sao Paulo, Sao Paulo, Brazil. Electronic address: jaqueytw@gmail.com., Kronenberger T; Department of Internal Medicine VIII, University Hospital Tübingen, Tübingen, Germany. Electronic address: kronenberger7@gmail.com., Cerda A; Center of Excellence in Translational Medicine, BIOREN, Department of Basic Sciences, Universidad de La Frontera, Temuco, Chile. Electronic address: alvaro.cerda@ufrontera.cl., Lin-Wang HT; Institute Dante Pazzanese of Cardiology, Sao Paulo, Brazil. Electronic address: pesquisalin@yahoo.com.br., Garofalo AR; Institute Dante Pazzanese of Cardiology, Sao Paulo, Brazil. Electronic address: adrianaregarofalo@gmail.com., Fajardo CM; School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil. Electronic address: cris.mf01@gmail.com., Hirata RDC; School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil. Electronic address: rosariohirata@usp.br., Hirata MH; School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil. Electronic address: mhhirata@usp.br. |
| المصدر: | Research in social & administrative pharmacy : RSAP [Res Social Adm Pharm] 2021 Jul; Vol. 17 (7), pp. 1347-1355. Date of Electronic Publication: 2020 Oct 29. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 101231974 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1934-8150 (Electronic) Linking ISSN: 15517411 NLM ISO Abbreviation: Res Social Adm Pharm Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: New York, NY : Elsevier |
| مواضيع طبية MeSH: | Hyperlipoproteinemia Type II*/drug therapy , Hyperlipoproteinemia Type II*/genetics, Brazil ; Epigenomics ; Genomics ; Humans ; Molecular Docking Simulation ; Pharmacogenetics |
| مستخلص: | Background: Familial hypercholesterolemia (FH) is a genetic disease that affects millions of people worldwide. Objectives: The study protocol FHBGEP was design to investigate the main genomic, epigenomic, and pharmacogenomic factors associated with FH and polygenic hypercholesterolemia (PH). Methods: FH patients will be enrolled at six research centers in Brazil. An exon-targeted gene strategy will be used to sequence a panel of 84 genes related to FH, PH, pharmacogenomics and coronary artery disease. Variants in coding and regulatory regions will be identified using a proposed variant discovery pipeline and classified according to the American College Medical Genetics guidelines. Functional effects of variants in FH-related genes will be investigated by in vitro studies using lymphocytes and cell lines (HepG2, HUVEC and HEK293FT), CRISPR/Cas9 mutagenesis, luciferase reporter assay and other technologies. Functional studies in silico, such as molecular docking, molecular dynamics, and conformational analysis, will be used to explore the impact of novel variants on protein structure and function. DNA methylation profile and differential expression of circulating non-coding RNAs (miRNAs and lncRNAs) will be analyzed in FH patients and normolipidemic subjects (control group). The influence of genomic and epigenomic factors on metabolic and inflammatory status will be analyzed in FH patients. Pharmacogenomic studies will be conducted to investigate the influence of genomic and epigenomic factors on response to statins in FH patients. Summary: The FHBGEP protocol has the potential to elucidate the genetic basis and molecular mechanisms involved in the pathophysiology of FH and PH, particularly in the Brazilian population. This pioneering approach includes genomic, epigenomic and functional studies, which results will contribute to the improvement of the diagnosis, prognosis and personalized therapy of FH patients. (Copyright © 2020 Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Epigenomics; Familial hypercholesterolemia; Genomics; Pharmacogenomics; Polygenic hypercholesterolemia |
| تواريخ الأحداث: | Date Created: 20201101 Date Completed: 20210802 Latest Revision: 20210802 |
| رمز التحديث: | 20240829 |
| DOI: | 10.1016/j.sapharm.2020.10.007 |
| PMID: | 33129683 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1934-8150 |
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| DOI: | 10.1016/j.sapharm.2020.10.007 |