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Olle Melander

Principal investigator

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Orthostatic hypotension and novel blood pressure-associated gene variants: Genetics of Postural Hemodynamics (GPH) Consortium.

Author

  • Artur Fedorowski
  • Nora Franceschini
  • Jennifer Brody
  • Chunyu Liu
  • Germaine C Verwoert
  • Eric Boerwinkle
  • David Couper
  • Kenneth M Rice
  • Jerome I Rotter
  • Francesco Mattace Raso
  • Andre Uitterlinden
  • Albert Hofman
  • Peter Almgren
  • Marketa Sjögren
  • Bo Hedblad
  • Martin G Larson
  • Christopher Newton-Cheh
  • Thomas J Wang
  • Kathryn M Rose
  • Bruce M Psaty
  • Daniel Levy
  • Jacqueline Witteman
  • Olle Melander

Summary, in English

Aims: Orthostatic hypotension (OH), an independent predictor of mortality and cardiovascular events, strongly correlates with hypertension. Recent genome-wide studies have identified new loci influencing blood pressure (BP) in populations, but their impact on OH remains unknown.Methods and resultsA total of 38 970 men and women of European ancestry from five population-based cohorts were included, of whom 2656 (6.8%) met the diagnostic criteria for OH (systolic/diastolic BP drop ≥20/10 mmHg within 3 min of standing). Thirty-one recently discovered BP-associated single nucleotide polymorphisms (SNPs) were examined using an additive genetic model and the major allele as referent. Relations between OH, orthostatic systolic BP response, and genetic variants were assessed by inverse variance-weighted meta-analysis. We found Bonferroni adjusted (P < 0.0016) significant evidence for association between OH and the EBF1 locus (rs11953630, per-minor-allele odds ratio, 95% confidence interval: 0.90, 0.85-0.96; P = 0.001), and nominal evidence (P < 0.05) for CYP17A1 (rs11191548: 0.85, 0.75-0.95; P = 0.005), and NPR3-C5orf23 (rs1173771: 0.92, 0.87-0.98; P= 0.009) loci. Among subjects not taking BP-lowering drugs, three SNPs within the NPPA/NPPB locus were nominally associated with increased risk of OH (rs17367504: 1.13, 1.02-1.24; P = 0.02, rs198358: 1.10, 1.01-1.20; P = 0.04, and rs5068: 1.22, 1.04-1.43; P = 0.01). Moreover, an ADM variant was nominally associated with continuous orthostatic systolic BP response in the adjusted model (P= 0.04).ConclusionThe overall association between common gene variants in BP loci and OH was generally weak and the direction of effect inconsistent with resting BP findings. These results suggest that OH and resting BP share few genetic components.

Department/s

  • Cardiovascular Research - Hypertension
  • Genomics, Diabetes and Endocrinology
  • Cardiovascular Research - Epidemiology
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year

2012

Language

English

Pages

2331-2341

Publication/Series

European Heart Journal

Volume

33

Issue

18

Document type

Journal article

Publisher

Oxford University Press

Topic

  • Cardiac and Cardiovascular Systems

Status

Published

Research group

  • Cardiovascular Research - Hypertension
  • Genomics, Diabetes and Endocrinology
  • Cardiovascular Research - Epidemiology

ISBN/ISSN/Other

  • ISSN: 1522-9645