Association study between a genetic polymorphism in aldosterone sinthase and resistance to anti-hypertension treatment / Estudo de associação entre polimorfismo no gene da aldosterona sintase e resistencia ao tratamento anti-hipertensivo

AUTOR(ES)
DATA DE PUBLICAÇÃO

2008

RESUMO

Introduction: Resistant hypertension is characterized by elevated blood pressure concurrent with the use of 3 different anti-hypertensive drugs, being one of them a diuretic. There are genetic factors that interfere in the arterial pressure control system and may have a significant role in resistant hypertension. Renin-Angiotensin-Aldosterone System plays a major role in hypertension genesis, therefore the systems that control the production and transport of aldosterone are interesting targets for genetic association studies. This work presents the study of a polymorphism (-344 C/T) in CYP11b2 gene. This gene translates aldosterone synthase, an enzyme responsible for endogenous synthesis of aldosterone on adrenal glands. A secondary study on a polymorphism (3435C/T) in MDR-1 gene was performed. This gene translates p-glicoprotein, an efflux-pump related to several drug resistance phenotypes. Recently it was reported that tissue uptake and excretion of aldosterone is mediated by p-glicoprotein. Objectives: The study aims to evaluate the association between allele T of CYP11b2 and resistance to anti-hypertension treatment. As a second objective it has been performed an initial evaluation of the influence of C allele of MDR-1 on resistant hypertension phenotype. Materials and Methods: In this study, 340 subjects were evaluated: 88 patients presented Refractory Arterial Hypertension (RAH), 142 were responsive to anti-hypertension treatment (RT), and the remaining was the control group (n=110). Blood samples were collected for laboratory examinations (plasmatic aldosterone, cortisol, renin) and DNA extraction. It was examined the carotid intima-media thickness (IMT) using ultra-sound, and carotid-femoral pulse wave velocity (PWV). DNA was extracted using the salting out method. CYP11b2 genotyping was performed through restriction fragment length polymorphism (polymerase chain reaction (PCR) followed by endonuclease digestion). PCR products were digested with Hae III enzyme. MDR-1 genotyping was performed through allele specific PCR. Results: It was found association between allele T of CYP11b2 and hypertension (p<0,005), but no difference has been detected between RT and RAH groups. No statistical difference was detected in plasmatic aldosterone, cortisol and renin concentrations, neither in PWV nor in IMT when compared C and T allele groups. It was found no relationship between alleleC of MDR-1 and hypertension, treated or resistant, although there was a significant association between allele C of this gene and elevated diastolic blood pressure in the RAH group. Conclusions: There is association between allele T of CYP11b2 gene and hypertension, but there is no relationship with pharmacological resistance to antihypertensive treatment. No influence was detected of allele T regarding clinical parameters or remodeling indicators. Allele C of MDR-1 gene seems to be associated with an elevated diastolic blood pressure in resistant hypertensive subjects

ASSUNTO(S)

aldosterona hipertensão farmacogenetica aldosterone pharmacogenetics hypertension

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