TY - JOUR
T1 - The functional c.-2G>C variant of the mineralocorticoid receptor modulates blood pressure, renin, and aldosterone levels
AU - Van Leeuwen, Nienke
AU - Caprio, Massimiliano
AU - Blaya, Carolina
AU - Fumeron, Frédéric
AU - Sartorato, Paola
AU - Ronconi, Vanessa
AU - Giacchetti, Gilberta
AU - Mantero, Franco
AU - Fernandes-Rosa, Fabio L.
AU - Simian, Christophe
AU - Peyrard, Sévrine
AU - Zitman, Frans G.
AU - Penninx, Brenda W J H
AU - De Kloet, E. Ron
AU - Azizi, Michel
AU - Jeunemaitre, Xavier
AU - Derijk, Roel H.
AU - Zennaro, Maria Christina
PY - 2010/11
Y1 - 2010/11
N2 - The mineralocorticoid receptor (MR) is essential in the regulation of volemia and blood pressure. Rare mutations in the MR gene cause type 1 pseudohypoaldosteronism and hypertension. In this study we characterized the common MR polymorphism c.-2G>C (rs2070951) in vitro and tested its influence on parameters related to blood pressure regulation and the renin-angiotensin system. In vitro studies showed that the G allele was associated with decreased MR protein levels and reduced transcriptional activation compared with the C allele. Association studies were performed with several outcome variables in 3 independent cohorts: a mild hypertensive group subjected to a salt-sensitivity test, a healthy normotensive group included in a crossover study to receive both a high and low Na/K diet, and a large cohort (The Netherlands Study of Depression and Anxiety), in which blood pressure was measured. Subjects with the GG genotype had significantly higher plasma renin levels both in the mild hypertensive group and in normal volunteers compared with homozygous C carriers. The GG genotype was also correlated with higher plasma aldosterone levels in healthy subjects. In both the mild hypertensive group and The Netherlands Study of Depression and Anxiety cohort the genotype GG was associated with higher systolic blood pressure in males. In conclusion, the G allele of the common functional genetic polymorphism c.-2G>C in the MR gene associates with increased activation of the renin-angiotensin-aldosterone axis and with increased blood pressure, probably related to decreased MR expression.
AB - The mineralocorticoid receptor (MR) is essential in the regulation of volemia and blood pressure. Rare mutations in the MR gene cause type 1 pseudohypoaldosteronism and hypertension. In this study we characterized the common MR polymorphism c.-2G>C (rs2070951) in vitro and tested its influence on parameters related to blood pressure regulation and the renin-angiotensin system. In vitro studies showed that the G allele was associated with decreased MR protein levels and reduced transcriptional activation compared with the C allele. Association studies were performed with several outcome variables in 3 independent cohorts: a mild hypertensive group subjected to a salt-sensitivity test, a healthy normotensive group included in a crossover study to receive both a high and low Na/K diet, and a large cohort (The Netherlands Study of Depression and Anxiety), in which blood pressure was measured. Subjects with the GG genotype had significantly higher plasma renin levels both in the mild hypertensive group and in normal volunteers compared with homozygous C carriers. The GG genotype was also correlated with higher plasma aldosterone levels in healthy subjects. In both the mild hypertensive group and The Netherlands Study of Depression and Anxiety cohort the genotype GG was associated with higher systolic blood pressure in males. In conclusion, the G allele of the common functional genetic polymorphism c.-2G>C in the MR gene associates with increased activation of the renin-angiotensin-aldosterone axis and with increased blood pressure, probably related to decreased MR expression.
KW - aldosterone
KW - hypertension
KW - mineralocorticoid
KW - nuclear receptor
KW - sodium balance
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U2 - 10.1161/HYPERTENSIONAHA.110.155630
DO - 10.1161/HYPERTENSIONAHA.110.155630
M3 - Article
C2 - 20855654
AN - SCOPUS:78149270394
VL - 56
SP - 995
EP - 1002
JO - Hypertension
JF - Hypertension
SN - 0194-911X
IS - 5
ER -