Dataset Information

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

ABSTRACT: Genome-wide association studies have linked CYP17A1 coding for the steroid hormone synthesizing enzyme 17?-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.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 17?-hydroxylase/17,20-lyase activity (ratio 1) and the other predominantly 17?-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.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.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.

SUBMITTER: Ackermann D

PROVIDER: S-EPMC4886492 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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

Ackermann Daniel D Pruijm Menno M Ponte Belen B Guessous Idris I Ehret Georg G Escher Geneviève G Dick Bernhard B Al-Alwan Heba H Vuistiner Philippe P Paccaud Fred F Burnier Michel M Péchère-Bertschi Antoinette A Martin Pierre-Yves PY Vogt Bruno B Mohaupt Markus M Bochud Murielle M

American journal of hypertension 20150820 4

<h4>Background</h4>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.<h4>Methods</h4>In the Swiss Kidney Project on Genes in Hypertension, day and night urinary excretions of steroid h ...[more]

PMID: 26297028

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Project description:BackgroundAmbulatory blood pressure (ABP) is consistently superior to clinic blood pressure (CBP) as a predictor of cardiovascular morbidity and mortality risk. A common perception is that ABP is usually lower than CBP. The relationship of the CBP minus ABP difference to age has not been examined in the United States.MethodsBetween 2005 and 2012, 888 healthy, employed, middle-aged (mean±SD age, 45±10.4 years) individuals (59% female, 7.4% black, 12% Hispanic) with screening BP <160/105 mm Hg and not taking antihypertensive medication completed 3 separate clinic BP assessments and a 24-hour ABP recording for the Masked Hypertension Study. The distributions of CBP, mean awake ABP (aABP), and the CBP-aABP difference in the full sample and by demographic characteristics were compared. Locally weighted scatterplot smoothing was used to model the relationship of the BP measures to age and body mass index. The prevalence of discrepancies in ABP- versus CBP-defined hypertension status-white-coat hypertension and masked hypertension-were also examined.ResultsAverage systolic/diastolic aABP (123.0/77.4±10.3/7.4 mm Hg) was significantly higher than the average of 9 CBP readings over 3 visits (116.0/75.4±11.6/7.7 mm Hg). aABP exceeded CBP by >10 mm Hg much more frequently than CBP exceeded aABP. The difference (aABP>CBP) was most pronounced in young adults and those with normal body mass index. The systolic difference progressively diminished, but did not disappear, at older ages and higher body mass indexes. The diastolic difference vanished around age 65 and reversed (CBP>aABP) for body mass index >32.5 kg/m2. Whereas 5.3% of participants were hypertensive by CBP, 19.2% were hypertensive by aABP; 15.7% of those with nonelevated CBP had masked hypertension.ConclusionsContrary to a widely held belief, based primarily on cohort studies of patients with elevated CBP, ABP is not usually lower than CBP, at least not among healthy, employed individuals. Furthermore, a substantial proportion of otherwise healthy individuals with nonelevated CBP have masked hypertension. Demonstrated CBP-aABP gradients, if confirmed in representative samples (eg, NHANES [National Health and Nutrition Examination Survey]), could provide guidance for primary care physicians as to when, for a given CBP, 24-hour ABP would be useful to identify or rule out masked hypertension.

Dataset Information

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

Publications

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

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