title: 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.
authors.affiliation: Department of Kinesiology, University of Connecticut, Storrs, Connecticut Linda.Pescatello@uconn.edu.|Institute for Systems Genomics, University of Connecticut, Storrs, Connecticut.
authors.forename: Linda S
authors.initials: LS
authors.lastname: Pescatello
authors.affiliation: Department of Statistics, University of Connecticut, Storrs, Connecticut.
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Schifano
authors.affiliation: School of Nursing, Yale University, New Haven, Connecticut.
authors.forename: Garrett I
authors.initials: GI
authors.lastname: Ash
authors.affiliation: Department of Kinesiology, University of Connecticut, Storrs, Connecticut.|Department of Preventive Cardiology, Hartford Hospital, Hartford, Connecticut.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Panza
authors.affiliation: Department of Kinesiology, University of Connecticut, Storrs, Connecticut.
authors.forename: Lauren
authors.initials: L
authors.lastname: Lamberti
authors.affiliation: Department of Statistics, University of Connecticut, Storrs, Connecticut.
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Chen
authors.affiliation: Department of Statistics, University of Connecticut, Storrs, Connecticut.
authors.forename: Ved
authors.initials: V
authors.lastname: Deshpande
authors.affiliation: Department of Kinesiology, University of Connecticut, Storrs, Connecticut.|Department of Preventive Cardiology, Hartford Hospital, Hartford, Connecticut.
authors.forename: Amanda
authors.initials: A
authors.lastname: Zaleski
authors.affiliation: Department of Physical Activity Sciences, Rio de Janeiro State University, Rio de Janeiro, Brazil.
authors.forename: Paulo
authors.initials: P
authors.lastname: Farinatti
authors.affiliation: Department of Kinesiology, University of Connecticut, Storrs, Connecticut.|Department of Preventive Cardiology, Hartford Hospital, Hartford, Connecticut.
authors.forename: Beth A
authors.initials: BA
authors.lastname: Taylor
authors.affiliation: Department of Preventive Cardiology, Hartford Hospital, Hartford, Connecticut.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Thompson
mesh_terms: D000328:Adult; D001741:Black or African American; D001794:Blood Pressure / Q000502:physiology; D018660:Blood Pressure Monitoring, Ambulatory / Q000379:methods; D002148:Calmodulin-Binding Proteins / Q000378:metabolism; D019405:Cytochrome P-450 CYP11B2 / Q000378:metabolism; D005080:Exercise Test / Q000379:methods; D017079:Exercise Tolerance / Q000235:genetics* / Q000502:physiology; D005091:Exons / Q000235:genetics*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D057774:Post-Exercise Hypotension / Q000378:metabolism / Q000503:physiopathology*; D044465:White People; D000099291:Adducins
chemical_list: D002148:Calmodulin-Binding Proteins; D019405:Cytochrome P-450 CYP11B2; D000099291:Adducins
keywords: Blood pressure; exercise; hypertension; polymorphism