FURIN variant associations with postexercise hypotension are intensity and race dependent

Physiol Rep. 2019 Feb;7(3):e13952. doi: 10.14814/phy2.13952.

Abstract

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.

Keywords: Blood Pressure; exercise; hypertension; polymorphism.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Bicycling
  • Black or African American / genetics*
  • Blood Pressure / genetics*
  • Case-Control Studies
  • Exercise*
  • Female
  • Furin / genetics*
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Hypertension / ethnology
  • Hypertension / genetics*
  • Hypertension / physiopathology
  • Hypotension / ethnology
  • Hypotension / genetics*
  • Hypotension / physiopathology
  • Male
  • Middle Aged
  • Obesity / ethnology
  • Obesity / genetics
  • Obesity / physiopathology
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Risk Factors
  • Time Factors
  • White People / genetics*
  • Young Adult

Substances

  • FURIN protein, human
  • Furin