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CYP17A1 Enzyme Activity Is Linked to Ambulatory Blood Pressure in a Family-Based Population Study

Ackermann, Daniel ; Pruijm, Menno ; Ponte, Belen ; Guessous, Idris ; Ehret, Georg ; Escher, Geneviève ; Dick, Bernhard ; Al-Alwan, Heba ; Vuistiner, Philippe ; Paccaud, Fred ; Burnier, Michel ; Péchère-Bertschi, Antoinette ; Martin, Pierre-Yves ; Vogt, Bruno ; Mohaupt, Markus ; Bochud, Murielle

In: American Journal of Hypertension, 2016, vol. 29, no. 4, p. 484-493

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    Titre
    • CYP17A1 Enzyme Activity Is Linked to Ambulatory Blood Pressure in a Family-Based Population Study
    Auteur
    • Ackermann, Daniel. University Clinic for Nephrology, Hypertension and Clinical Pharmacology, Inselspital, Bern University Hospital and University of Bern , Bern , Switzerland
    • Pruijm, Menno. Service of Nephrology, University Hospital of Lausanne (CHUV) , Lausanne , Switzerland
    • Ponte, Belen. Service of Nephrology, University Hospital of Geneva (HUG) , Geneva , Switzerland
    • Guessous, Idris. Institute of Social and Preventive Medicine (IUMSP), University of Lausanne , Lausanne , Switzerland
    • Ehret, Georg. Cardiology, Department of Specialties of Internal Medicine, University Hospital of Geneva (HUG) , Geneva , Switzerland
    • Escher, Geneviève. University Clinic for Nephrology, Hypertension and Clinical Pharmacology, Inselspital, Bern University Hospital and University of Bern , Bern , Switzerland
    • Dick, Bernhard. University Clinic for Nephrology, Hypertension and Clinical Pharmacology, Inselspital, Bern University Hospital and University of Bern , Bern , Switzerland
    • Al-Alwan, Heba. Institute of Social and Preventive Medicine (IUMSP), University of Lausanne , Lausanne , Switzerland
    • Vuistiner, Philippe. Institute of Social and Preventive Medicine (IUMSP), University of Lausanne , Lausanne , Switzerland
    • Paccaud, Fred. Institute of Social and Preventive Medicine (IUMSP), University of Lausanne , Lausanne , Switzerland
    • Burnier, Michel. Service of Nephrology, University Hospital of Lausanne (CHUV) , Lausanne , Switzerland
    • Péchère-Bertschi, Antoinette. Service of Endocrinology, Department of Specialties of Internal Medicine, University Hospital of Geneva (HUG) , Geneva , Switzerland .
    • Martin, Pierre-Yves. Service of Nephrology, University Hospital of Geneva (HUG) , Geneva , Switzerland
    • Vogt, Bruno. University Clinic for Nephrology, Hypertension and Clinical Pharmacology, Inselspital, Bern University Hospital and University of Bern , Bern , Switzerland
    • Mohaupt, Markus. University Clinic for Nephrology, Hypertension and Clinical Pharmacology, Inselspital, Bern University Hospital and University of Bern , Bern , Switzerland
    • Bochud, Murielle. Institute of Social and Preventive Medicine (IUMSP), University of Lausanne , Lausanne , Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • American Journal of Hypertension, 2016, vol. 29, no. 4, p. 484-493. Oxford University Press
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:331309
    Summary
    Abstract BACKGROUND Genome-wide association studies have linked CYP17A1 coding for the steroid hormone synthesizing enzyme 17α-hydroxylase (CYP17A1) to blood pressure (BP). We hypothesized that the genetic signal may translate into a correlation of ambulatory BP (ABP) with apparent CYP17A1 activity in a family-based population study and estimated the heritability of CYP17A1 activity. METHODS In the Swiss Kidney Project on Genes in Hypertension, day and night urinary excretions of steroid hormone metabolites were measured in 518 participants (220 men, 298 women), randomly selected from the general population. CYP17A1 activity was assessed by 2 ratios of urinary steroid metabolites: one estimating the combined 17α-hydroxylase/17,20-lyase activity (ratio 1) and the other predominantly 17α-hydroxylase activity (ratio 2). A mixed linear model was used to investigate the association of ABP with log-transformed CYP17A1 activities exploring effect modification by urinary sodium excretion. RESULTS Daytime ABP was positively associated with ratio 1 under conditions of high, but not low urinary sodium excretion ( P interaction <0.05). Ratio 2 was not associated with ABP. Heritability estimates (SE) for day and night CYP17A1 activities were 0.39 (0.10) and 0.40 (0.09) for ratio 1, and 0.71 (0.09) and 0.55 (0.09) for ratio 2 ( P values <0.001). CYP17A1 activities, assessed with ratio 1, were lower in older participants. CONCLUSIONS Low apparent CYP17A1 activity (assessed with ratio 1) is associated with elevated daytime ABP when salt intake is high. CYP17A1 activity is heritable and diminished in the elderly. These observations highlight the modifying effect of salt intake on the association of CYP17A1 with BP.