title: Modulation of aldosterone levels by -344 C/T CYP11B2 polymorphism and spironolactone use in resistant hypertension.
abstract: Interindividual variability in plasma aldosterone levels comprises environmental and genetic sources. Increased aldosterone levels have been associated with higher risk of hypertension and target-organ damage related to hypertension. Aldosterone excess and intravascular volume expansion are implicated in pathophysiology of resistant hypertension (RH). We sought to investigate whether -344 C/T polymorphism (rs1799998) in aldosterone synthase gene (CYP11B2) is associated with plasma aldosterone levels in patients with resistant hypertension. Sixty-two patients with resistant hypertension were enrolled in this cross-sectional study. Genotypes were obtained by allelic discrimination assay using real time polymerase chain reaction. Multivariable linear regression was used to identify whether TT genotype was a predictor of aldosterone levels. No differences in clinical and laboratorial parameters were found among genotype groups. We found an additive effect of the T allele on plasma aldosterone concentration in RH. Also, there was higher aldosterone levels in TT homozygous under use of spironolactone compared with C carriers and compared with TT subjects who was not under use of spironolactone. TT genotype and the use of spironolactone were significant predictors of aldosterone levels in RH subjects. Plasma aldosterone concentration is significantly associated with -344 C/T CYP11B2 polymorphism and with the treatment with spironolactone in resistant hypertensive subjects.
authors.affiliation: Laboratory of Cardiovascular Pharmacology, Faculty of Medical Sciences, University of Campinas, Campinas, SP, Brazil. Electronic address: fontana@unicamp.br.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Fontana
authors.affiliation: Laboratory of Cardiovascular Pharmacology, Faculty of Medical Sciences, University of Campinas, Campinas, SP, Brazil.
authors.forename: Ana Paula Cabral
authors.initials: AP
authors.lastname: de Faria
authors.affiliation: Laboratory of Cardiovascular Pharmacology, Faculty of Medical Sciences, University of Campinas, Campinas, SP, Brazil.
authors.forename: Natália Ruggeri
authors.initials: NR
authors.lastname: Barbaro
authors.affiliation: Laboratory of Cardiovascular Pharmacology, Faculty of Medical Sciences, University of Campinas, Campinas, SP, Brazil.
authors.forename: Andréa Rodrigues
authors.initials: AR
authors.lastname: Sabbatini
authors.affiliation: Laboratory of Cardiovascular Pharmacology, Faculty of Medical Sciences, University of Campinas, Campinas, SP, Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Modolo
authors.affiliation: Laboratory of Cardiovascular Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Lacchini
authors.affiliation: Laboratory of Cardiovascular Pharmacology, Faculty of Medical Sciences, University of Campinas, Campinas, SP, Brazil.
authors.forename: Heitor
authors.initials: H
authors.lastname: Moreno
mesh_terms: D000368:Aged; D000450:Aldosterone / Q000097:blood*; D000483:Alleles; D001794:Blood Pressure; D019405:Cytochrome P-450 CYP11B2 / Q000097:blood / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D013148:Spironolactone / Q000627:therapeutic use*
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000450:Aldosterone; D004247:DNA; D019405:Cytochrome P-450 CYP11B2
keywords: Mineralocorticoid receptor antagonists; aldosterone synthase and aldosterone breakthrough; refractory hypertension