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Genetic polymorphisms associated with cardiovascular outcomes and blood pressure control in resistant hypertension of INVEST-GENE substudy (the international Verapamil-Trandolapril study)

Grant number: 12/21782-4
Support Opportunities:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): March 11, 2013
Effective date (End): June 10, 2013
Field of knowledge:Biological Sciences - Pharmacology - Clinical Pharmacology
Principal Investigator:Heitor Moreno Junior
Grantee:Vanessa Fontana
Supervisor: Julie A. Johnson
Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Research place: University of Florida, Gainesville (UF), United States  
Associated to the scholarship:12/01386-7 - Impact of polymorphisms of adiponectin, leptin and aldosterone synthase on haemodynamic profile and anti-hypertensive response in resistant hypertension., BP.PD

Abstract

Resistant hypertension is defined as blood pressure that remains above goals in spite of concurrent use of 3 antihypertensive agents of different classes at optimal doses, including a diuretic drug. Indeed, patients whose blood pressure is controlled with use of 4 or more medications are considered resistant to treatment. These patients have high cardiovascular risk compared to patients with non-resistant hypertension. Treatment resistance involves multiple etiologies and pathways and the genetic background plays an important role. Genetic association studies have been shown that some genetic variants are associated with antihypertensive blood pressure response and with cardiovascular outcomes. However there are limited studies regarding genetic variations in cardiovascular outcomes and blood pressure control in resistant hypertension. We aim to evaluate the association between genetic variants with cardiovascular array and cardiovascular outcomes (death, myocardial infarction and stroke) in resistant hypertensive patients of INVEST-GENE study. The resistant hypertensive patients will be selected from the INVEST study population, and the genotypes previously obtained using the Illumina Human CVD bead chip will be analyzed for this population. Patients will be excluded if sample genotype call rates were below 95% and SNPs will be excluded if genotype call rates were below 90%. A Principal Component Analysis (PCA) will be performed in all subjects using an LD pruned dataset using the EIGENSTRAT method. All statistical analyses will be carried out using SAS 9.2 (SAS Institute) or PLINK. Hardy-Weinberg equilibrium will be evaluated using a Ç2 test. Only variants with minor allele frequency of > 0.05 will be included in the analysis. Logistic regression will be used to evaluate association of each variant individually and adjusting for age, gender, prior MI, prior heart failure, history of diabetes and principal components. (AU)

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