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Deep-targeted exon sequencing reveals renal polymorphisms associate with postexercise hypotension among African Americans.

ABSTRACT: We found variants from the Angiotensinogen-Converting Enzyme (ACE), Angiotensin Type 1 Receptor (AGTR1), Aldosterone Synthase (CYP11B2), and Adducin (ADD1) genes exhibited intensity-dependent associations with the ambulatory blood pressure (BP) response following acute exercise, or postexercise hypotension (PEH). In a validation cohort, we sequenced exons from these genes for their associations with PEH Obese (30.9 ± 3.6 kg m-2) adults (n = 23; 61% African Americans [AF], 39% Caucasian) 42.0 ± 9.8 years with hypertension (139.8 ± 10.4/84.6 ± 6.2 mmHg) completed three random experiments: bouts of vigorous and moderate intensity cycling and control. Subjects wore an ambulatory BP monitor for 19 h. We performed deep-targeted exon sequencing using the Illumina TruSeq Custom Amplicon kit. Variant genotypes were coded as number of minor alleles (#MA) and selected for further statistical analysis based upon Bonferonni or Benjamini-Yekutieli multiple testing corrected p-values under time adjusted linear models for 19 hourly BP measurements per subject. After vigorous intensity over 19 h among ACE, AGTR1, CYP11B2, and ADD1 variants passing multiple testing thresholds, as the #MA increased, systolic (SBP) and/or diastolic BP decreased 12 mmHg (P = 4.5E-05) to 30 mmHg (P = 6.4E-04) among AF only. In contrast, after moderate intensity over 19 h among ACE and CYP11B2 variants passing multiple testing thresholds, as the #MA increased, SBP increased 21 mmHg (P = 8.0E-04) to 22 mmHg (P = 8.2E-04) among AF only. In this replication study, ACE, AGTR1, CYP11B2, and ADD1 variants exhibited associations with PEH after vigorous, but not moderate intensity exercise among AF only. Renal variants should be explored further with a multi-level "omics" approach for associations with PEH among a large, ethnically diverse sample of adults with hypertension.

SUBMITTER: Pescatello LS

PROVIDER: S-EPMC5064144 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Deep-targeted exon sequencing reveals renal polymorphisms associate with postexercise hypotension among African Americans.

Pescatello Linda S LS Schifano Elizabeth D ED Ash Garrett I GI Panza Gregory A GA Lamberti Lauren L Chen Ming-Hui MH Deshpande Ved V Zaleski Amanda A Farinatti Paulo P Taylor Beth A BA Thompson Paul D PD

Physiological reports 20161010 19

We found variants from the Angiotensinogen-Converting Enzyme (ACE), Angiotensin Type 1 Receptor (AGTR1), Aldosterone Synthase (CYP11B2), and Adducin (ADD1) genes exhibited intensity-dependent associations with the ambulatory blood pressure (BP) response following acute exercise, or postexercise hypotension (PEH). In a validation cohort, we sequenced exons from these genes for their associations with PEH Obese (30.9 ± 3.6 kg m<sup>-2</sup>) adults (n = 23; 61% African Americans [AF], 39% Caucasia ...[more]

PMID: 27940662

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Project description:IntroductionHigh salt intake is a widespread cardiovascular risk factor with systemic effects. These effects include an expansion of plasma volume, which may interfere with postexercise hypotension (PEH). However, the effects of high salt intake on central and peripheral indices of PEH remain unknown. We tested the hypothesis that high salt intake would attenuate central and peripheral PEH.MethodsNineteen healthy adults (7 female/12 male; age, 25 ± 4 yr; body mass index, 23.3 ± 2.2 kg·m; V[Combining Dot Above]O2peak, 41.6 ± 8.7 mL·min·kg; systolic blood pressure (BP), 112 ± 9 mm Hg; diastolic BP, 65 ± 9 mm Hg) participated in this double-blind, randomized, placebo-controlled crossover study. Participants were asked to maintain a 2300 mg·d sodium diet for 10 d on two occasions separated by ≥2 wk. Total salt intake was manipulated via ingestion of capsules containing either table salt (3900 mg·d) or placebo (dextrose) during each diet. On the 10th day, participants completed 50 min of cycling at 60% V[Combining Dot Above]O2peak. A subset of participants (n = 8) completed 60 min of seated rest (sham trial). Beat-to-beat BP was measured in-laboratory for 60 min after exercise via finger photoplethysmography. Brachial and central BPs were measured for 24 h after exercise via ambulatory BP monitor.ResultsTen days of high salt intake increased urinary sodium excretion (134 ± 70 (dextrose) vs 284 ± 74 mmol per 24 h (salt), P < 0.001), expanded plasma volume (7.2% ± 10.8%), and abolished PEH during in-laboratory BP monitoring (main effect of diet, P < 0.001). Ambulatory systolic BPs were higher for 12 h after exercise during the salt and sham trials compared with the dextrose trial (average change, 3.6 ± 2.1 mm Hg (dextrose), 9.9 ± 1.4 mm Hg (salt), 9.8 ± 2.5 mm Hg (sham); P = 0.01). Ambulatory central systolic BP was also higher during the salt trial compared with dextrose trial.ConclusionHigh salt intake attenuates peripheral and central PEH, potentially reducing the beneficial cardiovascular effects of acute aerobic exercise.

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Deep-targeted exon sequencing reveals renal polymorphisms associate with postexercise hypotension among African Americans.

Publications

Deep-targeted exon sequencing reveals renal polymorphisms associate with postexercise hypotension among African Americans.

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