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 (2015). CYP17A1 Enzyme Activity Is Linked to Ambulatory Blood Pressure in a Family-Based Population Study. American journal of hypertension, 29(4), pp. 484-493. Oxford University Press 10.1093/ajh/hpv138

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Nephrologie / Hypertonie

UniBE Contributor:

Ackermann, Daniel; Escher, Geneviève; Dick, Bernhard; Vogt, Bruno and Mohaupt, Markus

Subjects:

600 Technology > 610 Medicine & health
500 Science
500 Science > 570 Life sciences; biology

ISSN:

0895-7061

Publisher:

Oxford University Press

Language:

English

Submitter:

Daniel Ackermann

Date Deposited:

01 Mar 2016 13:52

Last Modified:

11 Jan 2017 12:09

Publisher DOI:

10.1093/ajh/hpv138

PubMed ID:

26297028

Uncontrolled Keywords:

CYP17A1; aging; blood pressure; heritability; hypertension; salt; steroids

BORIS DOI:

10.7892/boris.75819

URI:

https://boris.unibe.ch/id/eprint/75819

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