Open AccessDeep‐targeted exon sequencing reveals renal polymorphisms associate with postexercise hypotension among African Americans
Author(s) -
Pescatello Linda S.,
Schifano Elizabeth D.,
Ash Garrett I.,
Panza Gregory A.,
Lamberti Lauren,
Chen MingHui,
Deshpande Ved,
Zaleski Amanda,
Farinatti Paulo,
Taylor Beth A.,
Thompson Paul D.
Publication year - 2016
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.12992
Subject(s) - medicine , ambulatory blood pressure , blood pressure , exon , ambulatory , endocrinology , cardiology , genetics , biology , gene
We found variants from the Angiotensinogen‐Converting Enzyme ( ACE ), Angiotensin Type 1 Receptor ( AGTR 1 ), Aldosterone Synthase ( CYP 11B2 ), and Adducin ( ADD 1 ) 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 , AGTR 1 , CYP 11B2 , and ADD 1 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 CYP 11B2 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 , AGTR 1 , CYP 11B2 , and ADD 1 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.