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A multilocus genetic risk score is associated with arterial stiffness in hypertensive patients : The CARE NORTH study

Polonis, Katarzyna ; Hoffmann, Michal ; Szyndler, Anna ; Wolf, Jacek ; Nowak, Robert ; Becari, Christiane ; Laurent, Stephane ; Boutouyrie, Pierre ; Melander, Olle LU orcid and Narkiewicz, Krzysztof (2018) In Journal of Hypertension 36(9). p.1882-1888
Abstract

Introduction: Arterial stiffness is recognized as an intermediate phenotype and predictor of cardiovascular disease. Arterial stiffness is complex in origin with contributions from lifestyle and genetic factors. However, the association between single nucleotide polymorphisms (SNPs) and arterial stiffness remains unclear. Objective: The aim is to assess whether a multilocus genetic risk score (GRS), composed of selected SNPs linked to cardiovascular traits and outcomes, is associated with arterial stiffness in patients with hypertension. Design and methods: This study included 730 participants derived from the CARE NORTH study. The arterial stiffness was evaluated by carotid-femoral pulse wave velocity (cfPWV). An adjusted linear... (More)

Introduction: Arterial stiffness is recognized as an intermediate phenotype and predictor of cardiovascular disease. Arterial stiffness is complex in origin with contributions from lifestyle and genetic factors. However, the association between single nucleotide polymorphisms (SNPs) and arterial stiffness remains unclear. Objective: The aim is to assess whether a multilocus genetic risk score (GRS), composed of selected SNPs linked to cardiovascular traits and outcomes, is associated with arterial stiffness in patients with hypertension. Design and methods: This study included 730 participants derived from the CARE NORTH study. The arterial stiffness was evaluated by carotid-femoral pulse wave velocity (cfPWV). An adjusted linear regression was used to evaluate the association between cfPWV and each individual SNP using multiple genetic models. The association between a constructed GRS and cfPWV was tested in an unadjusted and adjusted model. Results: We selected 13 SNPs found to be associated with cfPWV (P<.05): 6 SNPs in additive, 4 SNPs in recessive and 3 SNPs in dominant mode of inheritance. The GRS based on these SNPs was positively associated with cfPWV both in unadjusted and adjusted models (β = 0.2m/s, 95% CI 0.11-0.29, P - 7.6 × 10-6 and β = 0.22 m/s, 95% CI 0.15-0.28, P=1.4 × 10-10, respectively). The GRS explained an additional 3.6% cfPWV variance above clinical covariates. Conclusion: We demonstrate that the GRS composed of 13 SNPs related to cardiovascular phenotypes is associated with an increased arterial stiffness in hypertensive patients. Our findings may help to clarify genetic basis of arterial stiffening and provide insight into mechanisms underlying this phenotype.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Arterial stiffness, Genetic risk score, Hypertension, Pulse wave velocity
in
Journal of Hypertension
volume
36
issue
9
pages
7 pages
publisher
Lippincott Williams & Wilkins
external identifiers
  • scopus:85056609112
  • pmid:29878972
ISSN
0263-6352
DOI
10.1097/HJH.0000000000001773
language
English
LU publication?
yes
id
3458d49b-f7c0-47df-94b5-8b944a266ae5
date added to LUP
2018-11-28 09:58:05
date last changed
2024-04-15 17:38:40
@article{3458d49b-f7c0-47df-94b5-8b944a266ae5,
  abstract     = {{<p>Introduction: Arterial stiffness is recognized as an intermediate phenotype and predictor of cardiovascular disease. Arterial stiffness is complex in origin with contributions from lifestyle and genetic factors. However, the association between single nucleotide polymorphisms (SNPs) and arterial stiffness remains unclear. Objective: The aim is to assess whether a multilocus genetic risk score (GRS), composed of selected SNPs linked to cardiovascular traits and outcomes, is associated with arterial stiffness in patients with hypertension. Design and methods: This study included 730 participants derived from the CARE NORTH study. The arterial stiffness was evaluated by carotid-femoral pulse wave velocity (cfPWV). An adjusted linear regression was used to evaluate the association between cfPWV and each individual SNP using multiple genetic models. The association between a constructed GRS and cfPWV was tested in an unadjusted and adjusted model. Results: We selected 13 SNPs found to be associated with cfPWV (P&lt;.05): 6 SNPs in additive, 4 SNPs in recessive and 3 SNPs in dominant mode of inheritance. The GRS based on these SNPs was positively associated with cfPWV both in unadjusted and adjusted models (β = 0.2m/s, 95% CI 0.11-0.29, P - 7.6 × 10<sup>-6</sup> and β = 0.22 m/s, 95% CI 0.15-0.28, P=1.4 × 10<sup>-10</sup>, respectively). The GRS explained an additional 3.6% cfPWV variance above clinical covariates. Conclusion: We demonstrate that the GRS composed of 13 SNPs related to cardiovascular phenotypes is associated with an increased arterial stiffness in hypertensive patients. Our findings may help to clarify genetic basis of arterial stiffening and provide insight into mechanisms underlying this phenotype.</p>}},
  author       = {{Polonis, Katarzyna and Hoffmann, Michal and Szyndler, Anna and Wolf, Jacek and Nowak, Robert and Becari, Christiane and Laurent, Stephane and Boutouyrie, Pierre and Melander, Olle and Narkiewicz, Krzysztof}},
  issn         = {{0263-6352}},
  keywords     = {{Arterial stiffness; Genetic risk score; Hypertension; Pulse wave velocity}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{1882--1888}},
  publisher    = {{Lippincott Williams & Wilkins}},
  series       = {{Journal of Hypertension}},
  title        = {{A multilocus genetic risk score is associated with arterial stiffness in hypertensive patients : The CARE NORTH study}},
  url          = {{http://dx.doi.org/10.1097/HJH.0000000000001773}},
  doi          = {{10.1097/HJH.0000000000001773}},
  volume       = {{36}},
  year         = {{2018}},
}