Pharmacogenetics and pharmacometabolomics analyses for antihypertensive drugs

• Grant number: 13/24440-0
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: September 01, 2014
• End date: March 31, 2018
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Paulo Caleb Júnior de Lima Santos
• Grantee: Carolina Tosin Bueno
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 13/09295-3 - Pharmacogenetic of cardiovascular system drugs focusing on implementation, AP.JP

Abstract

Cardiovascular diseases are the main causes of death worldwide and the pharmacological treatment implementation has been one of the most responsible for reductions in morbidity and mortality recent decades. Some pharmacogenetic tests are available to healthcare professionals, and increasingly, the regulatory agencies understand the relationship pharmaco-genomics. In this project, beside in pharmacogenetic studies and, we will investigate the new field of research called pharrmacometabolomics. It can be conceptualized as a set of changes on metabolome resulting from pharmacological treatments and its approach can clarify mechanisms for variations to responses to treatment, or even understand how genetic alterations influence the responses. The main aims are: 1- to identify polymorphisms associated with efficacy in the treatment, adverse drug, and treatment resistance; 2- to identify metabolomic changes induced by the treatment, to associate metabolomic changes with responses to treatment, with adverse effects, with resistant hypertension, or with possible effects of the polymorphisms. Analyses of genotypes will be performed by Taqman® OpenArray® technology and metabolomic analyses will be performed by mass spectrometry. We will include: 1500 patients with hypertension who were followed for a period of 24 weeks and for metabolomics analysis, 300 samples will be evaluated. Our expected results may show: 1- for pharmacogenetic: the possibility of personalized treatment and identification of resistant hypertension could result, on clinical and epidemiological scenario, in a reduction of complications due to hypertension and cardiovascular mortality; 2- for metabolomic analysis: may clarify mechanisms for variations to responses to treatment, or even understand how genetic alterations influence the responses. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DE FARIA, HENRIQUE DIPE; BUENO, CAROLINA TOSIN; KRIEGER, JOSE EDUARDO; KRIEGER, EDUARDO MOACYR; PEREIRA, ALEXANDRE COSTA; JUNIOR LIMA SANTOS, PAULO CALEB; FIGUEIREDO, EDUARDO COSTA. Online extraction of antihypertensive drugs and their metabolites from untreated human serum samples using restricted access carbon nanotubes in a column switching liquid chromatography system. Journal of Chromatography A, v. 1528, p. 41-52, DEC 15 2017. (13/09295-3, 13/24440-0)

BUENO, CAROLINA TOSIN; PEREIRA, ALEXANDRE COSTA; SANTOS, HADASSA CAMPOS; GOMEZ GOMEZ, LUZ MARINA; VANCAN RUSSO HORIMOTO, ANDREA ROSELI; KRIEGER, EDUARDO MOACYR; KRIEGER, JOSE EDUARDO; LIMA SANTOS, PAULO CALEB JUNIOR. Association of the genetic ancestry with resistant hypertension in the ReHOT (Resistant Hypertension Optimal Treatment) randomized study. SCIENTIFIC REPORTS, v. 10, n. 1, JAN 30 2020. (13/09295-3, 13/24440-0)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

BUENO, Carolina Tosin. Pharmacometabolomic and genetic ancestry evaluation in hypertensive patients from a randomized clinical trial. 2018. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.