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Blood Pressure in Patients with Primary Aldosteronism Is Influenced by Bradykinin B₂ Receptor and -Adducin Gene Polymorphisms

Department of Medicine and Experimental Oncology (P.M., T.A.W., A.M., C.P., F.R., F.V.), Hypertension Unit, University of Torino, 10133 Torino, Italy; and Department of Medical and Surgical Sciences (F.F.), Division of Endocrinology, University of Padova, 35121 Padova, Italy

Address all correspondence and requests for reprints to: Dr. Paolo Mulatero, Department of Medicine and Experimental Oncology, Hypertension Unit, San Vito Hospital, Strada S. Vito 34, 10133 Torino, Italy. E-mail: . paolo.mulatero{at}libero.it

Abstract

Primary aldosteronism (PA) is the most common cause of endocrine hypertension. PA is most frequently presented as moderate to severe hypertension, but the clinical and biochemical features vary widely. The aim of our study was to identify genetic variants that influence the phenotype of patients with PA. We hypothesized that genetic variants potentially affecting aldosterone production (aldosterone synthase, CYP11B2), renal proximal tubule reabsorption (-adducin), or the mechanisms of counterbalance leading to vasodilatation and sodium excretion (bradykinin B₂-receptor, B₂R) could influence the clinical and biochemical characteristics of patients with PA. We studied three polymorphisms of these genes (C-344T of CYP11B2, G460W of -adducin, and C-58T of B₂R) in 167 primary aldosteronism patients (56 with aldosterone-producing adenoma and 111 with idiopathic hyperaldosteronism). B₂R and -adducin genotypes were strong independent predictors of both systolic and diastolic blood pressure levels; plasma renin activity and aldosterone also play a marginal role on BP levels. Body mass index, age, sex, and CYP11B2 genotype displayed no significant effect on the clinical parameters of our population. In particular, -adducin and B₂R polymorphisms accounted for 13.2% and 11.0% of the systolic and diastolic blood pressure variance, respectively. These data suggest that genetic variants of -adducin and the bradykinin B₂-R influence the blood pressure levels in patients with primary aldosteronism.

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