Open AccessDeep‐targeted sequencing of endothelial nitric oxide synthase gene exons uncovers exercise intensity and ethnicity‐dependent associations with post‐exercise hypotension
Author(s) -
Pescatello Linda S.,
Schifano Elizabeth D.,
Ash Garrett I.,
Panza Gregory A.,
Corso Lauren M. L.,
Chen MingHui,
Deshpande Ved,
Zaleski Amanda,
Cilhoroz Burak,
Farinatti Paulo,
Taylor Beth A.,
O'Neill Rachel J.,
Thompson Paul D.
Publication year - 2017
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.13510
Subject(s) - medicine , exon , ambulatory blood pressure , blood pressure , ambulatory , diastole , cardiology , endocrinology , genetics , gene , biology
In previous studies, we found an endothelial nitric oxide synthase gene ( NOS 3 ) variant rs2070744 associated with the ambulatory blood pressure ( BP ) response following bouts of moderate and vigorous intensity acute exercise, termed post‐exercise hypotension ( PEH ). In a validation cohort, we sequenced NOS 3 exons for associations with PEH . Obese (30.9 ± 3.6 kg . m −2 ) African American ( n = 14) [ AF ] and Caucasian ( n = 9) adults 42.0 ± 9.8 years with hypertension (139.8 ± 10.4/84.6 ± 6.2 mmHg) performed three random experiments: bouts of vigorous and moderate intensity cycling and control. Subjects were attached to an ambulatory BP monitor for 19 h. We performed deep‐targeted exon sequencing with the Illumina TruSeq Custom Amplicon kit. Variant genotypes were coded as number of minor alleles (# MA ) and selected for additional statistical analysis based upon Bonferonni or Benjamini–Yekutieli multiple testing‐corrected P ‐values under time‐adjusted linear models for 19 hourly BP measurements for each subject. After vigorous intensity over 19 h, among NOS 3 variants passing multiple testing thresholds, as the # MA increased in rs891512 ( P = 6.4E‐04), rs867225 ( P = 6.5E‐04), rs743507 ( P = 2.6E‐06), and rs41483644 ( P = 2.4E‐04), systolic ( SBP ) decreased from 17.5 to 33.7 mmHg; and in rs891512 ( P = 9.7E‐05), rs867225 ( P = 2.6E‐05), rs41483644 ( P = 1.6E‐03), rs3730009 ( P = 2.6E‐04), and rs77325852 ( P = 5.6E‐04), diastolic BP decreased from 11.1 mmHg to 20.3 mmHg among AF only. In contrast, after moderate intensity over 19 h in NOS 3 rs3918164, as the # MA increased, SBP increased by 16.6 mmHg ( P = 2.4E‐04) among AF only. NOS 3 variants exhibited associations with PEH after vigorous, but not moderate intensity exercise among AF only. NOS 3 should be studied further for its effects on PEH in a large, ethnically diverse sample of adults with hypertension to confirm our findings.