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

Fedorowski, Artur LU ; Franceschini, Nora; Brody, Jennifer; Liu, Chunyu; Verwoert, Germaine C; Boerwinkle, Eric; Couper, David; Rice, Kenneth M; Rotter, Jerome I and Raso, Francesco Mattace, et al. (2012) In European Heart Journal 33(18). p.2331-2341
Abstract
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... (More)
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. (Less)
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Contribution to journal
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European Heart Journal
volume
33
issue
18
pages
2331 - 2341
publisher
Oxford University Press
external identifiers
  • WOS:000308886500014
  • PMID:22504314
  • Scopus:84866368524
ISSN
1522-9645
DOI
10.1093/eurheartj/ehs058
language
English
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yes
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2d3a29ba-59b1-46b5-9fc2-8fac9fef9def (old id 2519391)
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http://www.ncbi.nlm.nih.gov/pubmed/22504314?dopt=Abstract
date added to LUP
2012-05-06 17:44:23
date last changed
2016-11-13 04:30:07
@misc{2d3a29ba-59b1-46b5-9fc2-8fac9fef9def,
  abstract     = {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 &lt; 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 &lt; 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.},
  author       = {Fedorowski, Artur and Franceschini, Nora and Brody, Jennifer and Liu, Chunyu and Verwoert, Germaine C and Boerwinkle, Eric and Couper, David and Rice, Kenneth M and Rotter, Jerome I and Raso, Francesco Mattace and Uitterlinden, Andre and Hofman, Albert and Almgren, Peter and Sjögren, Marketa and Hedblad, Bo and Larson, Martin G and Newton-Cheh, Christopher and Wang, Thomas J and Rose, Kathryn M and Psaty, Bruce M and Levy, Daniel and Witteman, Jacqueline and Melander, Olle},
  issn         = {1522-9645},
  language     = {eng},
  number       = {18},
  pages        = {2331--2341},
  publisher    = {ARRAY(0xb6efd10)},
  series       = {European Heart Journal},
  title        = {Orthostatic hypotension and novel blood pressure-associated gene variants: Genetics of Postural Hemodynamics (GPH) Consortium.},
  url          = {http://dx.doi.org/10.1093/eurheartj/ehs058},
  volume       = {33},
  year         = {2012},
}