FURIN variant associations with postexercise hypotension are intensity and race dependent.

FURIN is a proprotein convertase subtilisin/kexin enzyme important in pro-renin receptor processing, and FURIN (furin, paired basic amino acid cleaving enzyme) variants are involved in multiple aspects of blood pressure (BP) regulation. Therefore, we examined associations among FURIN variants and the immediate blood pressure (BP) response to bouts of aerobic exercise, termed postexercise hypotension (PEH). Obese (30.9 ± 3.6 kg  m-2 ) Black- (n = 14) and White- (n = 9) adults 42.0 ± 9.8 year with hypertension (139.8 ± 10.4/84.6 ± 6.2 mmHg) performed three random experiments: bouts of vigorous (VIGOROUS) and moderate (MODERATE) intensity cycling and control. Subjects were then attached to an ambulatory BP monitor for 19 h. We performed deep-targeted exon sequencing with the Illumina TruSeq Custom Amplicon kit. FURIN genotypes were coded as the 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. After VIGOROUS over 19 h, as FURIN #MA increased in rs12917264 (P = 2.4E-04) and rs75493298 (P = 6.4E-04), systolic BP (SBP) decreased 30.4-33.7 mmHg; and in rs12917264 (P = 1.6E-03) and rs75493298 (P = 9.7E-05), diastolic BP (DBP) decreased 17.6-20.3 mmHg among Blacks only. In addition, after MODERATE over 19 h in FURIN rs74037507 (P = 8.0E-04), as #MA increased, SBP increased 20.8 mmHg among Blacks only. Whereas, after MODERATE over the awake hours in FURIN rs1573644 (P = 6.2E-04), as #MA increased, DBP decreased 12.5 mmHg among Whites only. FURIN appears to exhibit intensity and race-dependent associations with PEH that merit further exploration among a larger, ethnically diverse sample of adults with hypertension.

Deep-targeted sequencing of endothelial nitric oxide synthase gene exons uncovers exercise intensity and ethnicity-dependent associations with post-exercise hypotension.

In previous studies, we found an endothelial nitric oxide synthase gene (NOS3) 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 NOS3 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 NOS3 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 NOS3 rs3918164, as the #MA increased, SBP increased by 16.6 mmHg (P = 2.4E-04) among AF only. NOS3 variants exhibited associations with PEH after vigorous, but not moderate intensity exercise among AF only. NOS3 should be studied further for its effects on PEH in a large, ethnically diverse sample of adults with hypertension to confirm our findings.

The antihypertensive effects of aerobic versus isometric handgrip resistance exercise.

BACKGROUND: Aerobic exercise reduces blood pressure (BP) on average 5-7 mmHg among those with hypertension; limited evidence suggests similar or even greater BP benefits may result from isometric handgrip (IHG) resistance exercise. METHOD: We conducted a randomized controlled trial investigating the antihypertensive effects of an acute bout of aerobic compared with IHG exercise in the same individuals. Middle-aged adults (n = 27) with prehypertension and obesity randomly completed three experiments: aerobic (60% peak oxygen uptake, 30 min); IHG (30% maximum voluntary contraction, 4 × 2 min bilateral); and nonexercise control. Study participants were assessed for carotid-femoral pulse wave velocity pre and post exercise, and left the laboratory wearing an ambulatory BP monitor. RESULTS: SBP and DBP were lower after aerobic versus IHG (4.8 ±â€Š1.8/3.1 ±â€Š1.3 mmHg, P = 0.01/0.04) and control (5.6 ±â€Š1.8/3.6 ±â€Š1.3 mmHg, P = 0.02/0.04) over the awake hours, with no difference between IHG versus control (P = 0.80/0.83). Pulse wave velocity changes following acute exercise did not differ by modality (aerobic increased 0.01 ±â€Š0.21 ms, IHG decreased 0.06 ±â€Š0.15 ms, control increased 0.25 ±â€Š0.17 ms, P > 0.05). A subset of participants then completed either 8 weeks of aerobic or IHG training. Awake SBP was lower after versus before aerobic training (7.6 ±â€Š3.1 mmHg, P = 0.02), whereas sleep DBP was higher after IHG training (7.7 ±â€Š2.3 mmHg, P = 0.02). CONCLUSION: Our findings did not support IHG as antihypertensive therapy but that aerobic exercise should continue to be recommended as the primary exercise modality for its immediate and sustained BP benefits.

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

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.

Obesity-Related Genetic Variants and their Associations with Physical Activity.

BACKGROUND: Meta-analysis of genome-wide association studies identified obesity-related genetic variants. Due to the pleiotropic effects of related phenotypes, we tested six of these obesity-related genetic variants for their association with physical activity: fat mass and obesity-associated (FTO)(rs9939609)T>A, potassium channel tetramerization domain containing (KCTD15) (rs11084753)G>A, melanocortin receptor4 (MC4R)(rs17782313)T>C, neuronal growth regulator 1 (NEGR1)(rs2815752)A>G, SH2B adapter protein 1 (SH2B1)(rs7498665)A>G, and transmembrane protein18 (TMEM18)(rs6548238)C>T. METHOD: European-American women (n = 263) and men (n = 229) (23.5 ± 0.3 years, 24.6 ± 0.2 kg/m2) were genotyped and completed the Paffenbarger physical activity Questionnaire. Physical activity volume in metabolic energy equivalents [MET]-hour/week was derived from the summed time spent (hour/week) times the given MET value for vigorous, moderate, and light intensity physical activity, and sitting and sleeping, respectively. Multivariable adjusted [(age, sex, and body mass index (BMI)] linear regression tested associations among genotype (dominant/recessive model) and the log of physical activity volume. RESULT: MC4R (rs17782313)T>C explained 1.1 % (p = 0.02), TMEM18(rs6548238)C>T 1.2 % (p = 0.01), and SH2B1 (rs7498665)A>G 0.6 % (p = 0.08) of the variability in physical activity volume. Subjects with the MC4R C allele spent 3.5 % less MET-hour/week than those with the TT genotype (p = 0.02). Subjects with the TMEM18 T allele spent 4.1 % less MET-hour/week than those with the CC genotype (p = 0.01). Finally, subjects with the SH2B1 GG genotype spent 3.6 % less MET-hour/week than A allele carriers (p = 0.08). CONCLUSION: Our findings suggest a shared genetic influence among some obesity-related gene loci and physical activity phenotypes that should be explored further. Physical activity volume differences by genotype have public health importance equating to 11-13 lb weight difference annually.