NDT Advance Access originally published online on January 16, 2009
Nephrology Dialysis Transplantation 2009 24(6):1870-1875; doi:10.1093/ndt/gfn763
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High aldosterone-to-renin variants of CYP11B2 and pregnancy outcome
1 Department of Nephrology/Hypertension 2 Department of Obstetrics and Gynecology, University of Bern, Berne, Switzerland
Correspondence and offprint requests to: Markus G. Mohaupt; E-mail: markus.mohaupt{at}insel.ch
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Abstract |
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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.
Keywords: aldosterone synthase; aldosterone; arterial hypertension; pre-eclampsia; pregnancy outcome
Received for publication: 26. 9.08
Accepted in revised form: 19.12.08
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