Online citations, reference lists, and bibliographies.
← Back to Search

Different Polymorphisms Of The Mineralocorticoid Receptor Gene Are Associated With Either Glucocorticoid Or Mineralocorticoid Levels In Hypertension.

B. Sun, B. Chamarthi, J. Williams, A. Krug, J. Lasky-Su, B. Raby, P. Hopkins, X. Jeunemaître, C. Ferri, G. Williams
Published 2012 · Biology, Medicine

Cite This
Download PDF
Analyze on Scholarcy
OBJECTIVE Both aldosterone and cortisol can activate the mineralocorticoid receptor (MR). Polymorphisms in the MR gene have been inconsistently shown to be associated with risk of hypertension and aldosterone and cortisol levels. The purpose of this project was to investigate the association of MR gene variants with serum aldosterone and a previously identified hypertension subgroup with higher urinary free cortisol (UFC) levels (high-mode UFC) in a rigorously phenotyped Caucasian hypertensive cohort. MATERIALS AND METHODS A haplotype-based tagging single nucleotide polymorphism (htSNP) association study was conducted in the HyperPATH cohort of 570 hypertensive Caucasian subjects on a salt-controlled diet. Haplotypes generated from 74 htSNP representing the common genetic variations of the entire MR gene were analyzed by comparing high- vs. normal-mode UFC groups and the association with serum aldosterone levels. RESULTS Of the observed 20 haplotype blocks, there were three main linkage disequilibrium (LD) regions with high recombination rates between adjacent regions. Overlaying gene structure on this LD map revealed that block 1-8 corresponded to exon 5-9 [ligand binding domain (LBD)], blocks 9-18 to exon 3-4 [DNA binding domain (DBD)], and block 19-20 to exon 1-2 (N-terminal domain). Haplotype association results showed that DBD-aligned LD blocks were associated with high-mode UFC status (global P values, 0.0004 to 0.05). The LBD-aligned LD blocks showed significant associations with serum aldosterone levels. CONCLUSIONS These findings imply that there may be differential functional importance of the DBD and LBD of the MR in the regulation of glucocorticoid and aldosterone levels in hypertensive subjects.
This paper references
Urinary free cortisol is not a biochemical marker of hypertension.
Paola M Krall (2007)
Elucidating the underlying molecular pathogenesis of NR3C2 mutants causing autosomal dominant pseudohypoaldosteronism type 1.
F. Riepe (2006)
Urinary Free Cortisol: An Intermediate Phenotype and a Potential Genetic Marker for a Salt-Resistant Subset of Essential Hypertension
D. Schteingart (2008)
The Tale of the Guinea Pig
J. Funder (1994)
Exclusion of corticosterone from epithelial mineralocorticoid receptors is insufficient for selectivity of aldosterone action: in vivo binding studies.
J. Funder (1996)
The Functional c.-2G>C Variant of the Mineralocorticoid Receptor Modulates Blood Pressure, Renin, and Aldosterone Levels
N. van Leeuwen (2010)
The coming out of the brain mineralocorticoid receptor
M. Joëls (2008)
A critical region in the mineralocorticoid receptor for aldosterone binding and activation by cortisol: evidence for a common mechanism governing ligand binding specificity in steroid hormone receptors.
F. Rogerson (2007)
Recurrence of the R947X mutation in unrelated families with autosomal dominant pseudohypoaldosteronism type 1: evidence for a mutational hot spot in the mineralocorticoid receptor gene.
F. Fernandes-Rosa (2006)
Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy.
D. Geller (2000)
Aldosterone and mineralocorticoid receptors in the cardiovascular system.
J. Funder (2010)
Aldosterone in Heart Disease
A. Mihailidou (2012)
The mineralocorticoid receptor: insights into its molecular and (patho)physiological biology
S. Viengchareun (2007)
Hormones and the Stressed Brain
E. R. Kloet (2004)
Association of a mineralocorticoid receptor gene polymorphism with hypertension in a Spanish population.
F. Martínez (2009)
Clinical and genetic correlates of serum aldosterone in the community: the Framingham Heart Study.
S. Kathiresan (2005)
Increased urinary free cortisol: a potential intermediate phenotype of essential hypertension.
W. Litchfield (1998)
A common polymorphism in the mineralocorticoid receptor modulates stress responsiveness.
R. Derijk (2006)
Raised urinary glucocorticoid and adrenal androgen precursors in the urine of young hypertensive patients: possible evidence for partial glucocorticoid resistance
W. Shamim (2001)
Human mineralocorticoid receptor (MR) gene haplotypes modulate MR expression and transactivation: Implication for the stress response
N. V. Leeuwen (2011)

This paper is referenced by
Semantic Scholar Logo Some data provided by SemanticScholar