High aldosterone-to-renin variants of CYP11B2 and pregnancy outcome

Escher, Geneviève; Cristiano, Martino; Causevic, Maja; Baumann, Marc; Frey, Felix J; Surbek, Daniel; Mohaupt, Markus G (2009). High aldosterone-to-renin variants of CYP11B2 and pregnancy outcome. Nephrology, dialysis, transplantation, 24(6), pp. 1870-5. Oxford: Oxford University Press 10.1093/ndt/gfn763

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BACKGROUND: Increased aldosterone concentrations and volume expansion of normal pregnancies are hallmarks of normal pregnancies and blunted in pre-eclampsia. Accordingly, we hypothesized an active mineralocorticoid system to protect from pre-eclampsia. METHODS: In pregnant women (normotensive n = 44; pre-eclamptic n = 48), blood pressure, urinary tetrahydro-aldosterone excretion and activating polymorphisms (SF-1 site and intron 2) of the aldosterone synthase gene (CYP11B2) were determined; 185 non-pregnant normotensive individuals served as control. Amino acid-changing polymorphisms of the DNA- and agonist-binding regions of the mineralocorticoid receptor were evaluated by RT-PCR, SSCP and sequencing. RESULTS: Urinary tetrahydro-aldosterone excretion was reduced in pre-eclampsia as compared to normal pregnancy (P < 0.05). It inversely correlated with blood pressure (r = 0.99, P < 0.04). Homozygosity for activating CYP11B2 polymorphisms was preferably present in normotensive as compared to pre-eclamptic pregnancies, identified (intron 2, P = 0.005; SF-1 site, P = 0.016). Two mutant haplotypes decreased the risk of developing pre-eclampsia (RR 0.16; CI 0.05-0.54; P < 0.001). In contrast, intron 2 wild type predisposed to pre-eclampsia (P < 0.0015). No functional mineralocorticoid receptor mutant has been observed. CONCLUSIONS: High aldosterone availability is associated with lower maternal blood pressure. In line with this observation, gain-of-function variants of the CYP11B2 reduce the risk of developing pre-eclampsia. Mutants of the mineralocorticoid receptor cannot explain the frequent syndrome of pre-eclampsia.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Nephrologie / Hypertonie
04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology > Centre of Competence for Psychosomatic Medicine
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Thoracic Surgery
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Gynaecology
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension

UniBE Contributor:

Escher, Geneviève; Cristiano, Martino; Causevic, Maja; Baumann, Marc; Frey, Felix Julius; Surbek, Daniel and Mohaupt, Markus

ISSN:

0931-0509

Publisher:

Oxford University Press

Language:

English

Submitter:

Markus Georg Mohaupt

Date Deposited:

04 Oct 2013 15:12

Last Modified:

27 Apr 2018 08:42

Publisher DOI:

10.1093/ndt/gfn763

PubMed ID:

19151144

Web of Science ID:

000266355500027

BORIS DOI:

10.7892/boris.31589

URI:

https://boris.unibe.ch/id/eprint/31589 (FactScience: 196205)

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