title: CYP17A1 Enzyme Activity Is Linked to Ambulatory Blood Pressure in a Family-Based Population Study.
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.
authors: University Clinic for Nephrology, Hypertension and Clinical Pharmacology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland; daniel.ackermann@insel.ch.
authors: Daniel
authors: D
authors: Ackermann
authors: Service of Nephrology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland;
authors: Menno
authors: M
authors: Pruijm
authors: Service of Nephrology, University Hospital of Geneva (HUG), Geneva, Switzerland;
authors: Belen
authors: B
authors: Ponte
authors: Institute of Social and Preventive Medicine (IUMSP), University of Lausanne, Lausanne, Switzerland;
authors: Idris
authors: I
authors: Guessous
authors: Cardiology, Department of Specialties of Internal Medicine, University Hospital of Geneva (HUG), Geneva, Switzerland;
authors: Georg
authors: G
authors: Ehret
authors: University Clinic for Nephrology, Hypertension and Clinical Pharmacology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland;
authors: Geneviève
authors: G
authors: Escher
authors: University Clinic for Nephrology, Hypertension and Clinical Pharmacology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland;
authors: Bernhard
authors: B
authors: Dick
authors: Institute of Social and Preventive Medicine (IUMSP), University of Lausanne, Lausanne, Switzerland;
authors: Heba
authors: H
authors: Al-Alwan
authors: Institute of Social and Preventive Medicine (IUMSP), University of Lausanne, Lausanne, Switzerland;
authors: Philippe
authors: P
authors: Vuistiner
authors: Institute of Social and Preventive Medicine (IUMSP), University of Lausanne, Lausanne, Switzerland;
authors: Fred
authors: F
authors: Paccaud
authors: Service of Nephrology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland;
authors: Michel
authors: M
authors: Burnier
authors: Service of Endocrinology, Department of Specialties of Internal Medicine, University Hospital of Geneva (HUG), Geneva, Switzerland.
authors: Antoinette
authors: A
authors: Péchère-Bertschi
authors: Service of Nephrology, University Hospital of Geneva (HUG), Geneva, Switzerland;
authors: Pierre-Yves
authors: PY
authors: Martin
authors: University Clinic for Nephrology, Hypertension and Clinical Pharmacology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland;
authors: Bruno
authors: B
authors: Vogt
authors: University Clinic for Nephrology, Hypertension and Clinical Pharmacology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland;
authors: Markus
authors: M
authors: Mohaupt
authors: Institute of Social and Preventive Medicine (IUMSP), University of Lausanne, Lausanne, Switzerland;
authors: Murielle
authors: M
authors: Bochud
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000652:urine; D001794:Blood Pressure / Q000235:genetics; D018660:Blood Pressure Monitoring, Ambulatory; D002940:Circadian Rhythm; D003430:Cross-Sectional Studies; D005260:Female; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D005838:Genotype; D040941:Heredity; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009318:Natriuresis; D010641:Phenotype; D012307:Risk Factors; D012964:Sodium / Q000652:urine; D017673:Sodium Chloride, Dietary / Q000009:adverse effects; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism*; D013256:Steroids / Q000652:urine; D013379:Substrate Specificity; D013557:Switzerland; D013997:Time Factors; D016482:Urinalysis; D055815:Young Adult
chemical_list: D015415:Biomarkers; D017673:Sodium Chloride, Dietary; D013256:Steroids; D012964:Sodium; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase
keywords: CYP17A1; aging; blood pressure; heritability; hypertension; salt; steroids.