Journal ArticleDOI
Associations between aldosterone synthase gene polymorphism and the adrenocortical function in males
A. Hautanena,L. Lankinen,M. Kupari,O. A. Jänne,Herman Adlercreutz,Heli Nikkila,Perrin C. White +6 more
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TLDR
Hautanen et al. as discussed by the authors examined the associations between these genetic variations and adrenocortical function in a cohort of Finnish males and concluded that polymorphisms in or near the aldosterone synthase gene are associated with variations in aldrone and 11-deoxycortisol production in males.Abstract:
. Hautanen A, Lankinen L, Kupari M, Janne OA, Adlercreutz H, Nikkila H, White PC (Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland. University of Texas Southwestern Medical Center, Dallas, TX, USA). Associations between aldosterone synthase gene polymorphism and the adrenocortical function in males. J Intern Med 1998; 244: 11–18.
Objectives
Two diallelic polymorphisms, one in the transcriptional regulatory region (promoter) and the other in the second intron, have been identified in the aldosterone synthase (CYP11B2) gene encoding aldosterone synthase, the enzyme catalysing the last steps of aldosterone biosynthesis. We have examined the associations between these genetic variations and adrenocortical function in a cohort of Finnish males.
Design
A cross-sectional study.
Setting
Helsinki University Central Hospital, Finland.
Subjects
Ninety-two males aged 30–55 years.
Main outcome measures
Basal adrenocortical function was assessed by measuring urinary excretion of aldosterone and cortisol. Functional activity was determined by responses of several adrenal steroids to dexamethasone suppression followed by ACTH stimulation. Polymerase chain reactions were used to identify the polymorphisms in the CYP11B2 gene.
Results
The –344TT genotype group in the CYP11B2 promoter had lower systolic blood pressures (P= 0.039), but higher urinary aldosterone excretion (P= 0.016), and 11-deoxycortisol responses to ACTH stimulation (P= 0.021) than the –344CC genotype group. Urinary aldosterone excretion (P= 0.033), 11-deoxycortisol (P= 0.026), and aldosterone (P= 0.013) responses to ACTH were higher in the intron 2 conversion than the nonconversion genotype groups.
Conclusions
Polymorphisms in or near the aldosterone synthase gene are associated with variations in aldosterone and 11-deoxycortisol production in males. This may modulate the activity of the renin–angiotensin system and thereby contribute to blood pressure regulation.read more
Citations
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Links between dietary salt intake, renal salt handling, blood pressure, and cardiovascular diseases.
TL;DR: Chronic exposure to a high-salt diet appears to be a major factor involved in the frequent occurrence of hypertension and cardiovascular diseases in human populations.
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Heritability of cooperative behavior in the trust game
David Cesarini,Christopher T. Dawes,James H. Fowler,Magnus Johannesson,Paul Lichtenstein,Björn Wallace +5 more
TL;DR: The results of two independently conceived and executed studies of monozygotic and dizygotic twins suggest that humans are endowed with genetic variation that influences the decision to invest, and to reciprocate investment, in the classic trust game.
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The new biology of aldosterone
TL;DR: The role of aldosterone as a key cardiovascular hormone is highlighted and the understanding of its role in determining adverse cardiovascular outcomes is extended.
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Genotype-Phenotype Relationships for the Renin-Angiotensin-Aldosterone System in a Normal Population
Françoise Paillard,Dominique Chansel,Eva Brand,Athanase Benetos,Frédérique Thomas,Stanislaw Czekalski,Raymond Ardaillou,Florent Soubrier +7 more
TL;DR: The renin-angiotensin-aldosterone system plays an important role in blood pressure regulation by influencing salt-water homeostasis and vascular tone, and the purpose of the present study was to search for associations of single nucleotide polymorphisms on 3 major candidate genes of this system with the plasma concentrations of the corresponding renin and Ang II components considered as quantitative phenotypes.
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Molecular Basis of Salt Sensitivity in Human Hypertension: Evaluation of Renin-Angiotensin-Aldosterone System Gene Polymorphisms
TL;DR: The BP response to high salt intake was different among genotypes of ACE I/D and 11&bgr;HSD G534A, suggesting that these polymorphisms may be potentially useful genetic markers of salt sensitivity.
References
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Journal ArticleDOI
A chimaeric 11 beta-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension.
Richard P. Lifton,Robert G. Dluhy,Michael Powers,Glenn M. Rich,Sandra Cook,Stanley Ulick,Jean-Marc Lalouel +6 more
TL;DR: This work demonstrates complete linkage of GRA in a large kindred to a gene duplication arising from unequal crossing over, fusing the 5' regulatory region of 11β-hydroxylase to the coding sequences of aldosterone synthase.
Journal ArticleDOI
Steroidogenic factor I, a key regulator of steroidogenic enzyme expression, is the mouse homolog of fushi tarazu-factor I.
TL;DR: The model that a steroidogenic cell-selective protein interacts with related promoter elements from three steroidogenic enzymes to regulate their coordinate expression is supported and a cDNA is isolate and characterize that very likely encodes this protein.
Journal ArticleDOI
Tissue effects of glucocorticoids.
John D. Baxter,Peter H. Forsham +1 more
TL;DR: As with cyclic AMP and other types of steroids, glucocorticoids may play a more important role in fetal cellular and tissue differentiation than previously appreciated.
Journal ArticleDOI
Characterization of two genes encoding human steroid 11 beta-hydroxylase (P-450(11) beta).
TL;DR: The putative proteins encoded by CYP11B1 and B2 each contain 503 amino acids including a 24-residue signal peptide and have sequences that are 93% identical to each other and 75% identicalto the predicted sequence of bovine P-450(11) beta.