Please use this identifier to cite or link to this item:
|Title:||The biological impact of blood pressure associated genetic variants in the natriuretic peptide receptor C gene on human vascular smooth muscle.|
Ng, Fu Liang
Warren, Helen R.
Munroe, Patricia B.
Hobbs, Adrian J.
Caulfield, Mark J.
|Publisher:||Oxford University Press (OUP)|
|Citation:||Human Molecular Genetics, 2017|
|Abstract:||Elevated blood pressure (BP) is a major global risk factor for cardiovascular disease. Genome-wide association studies have identified several genetic variants at the NPR3 locus associated with BP, but the functional impact of these variants remains to be determined. Here we confirmed, by a genome-wide association study within UK Biobank, the existence of two independent BP-related signals within NPR3 locus. Using human primary vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) from different individuals, we found that the BP-elevating alleles within one linkage disequilibrium block identified by the sentinel variant rs1173771 was associated with lower endogenous NPR3 mRNA and protein levels in VSMCs, together with reduced levels in open chromatin and nuclear protein binding. The BP-elevating alleles also increased VSMC proliferation, angiotensin II-induced calcium flux and cell contraction. However, an analogous genotype-dependent association was not observed in vascular ECs. Our study identifies novel, putative mechanisms for BP-associated variants at the NPR3 locus to elevate BP, further strengthening the case for targeting NPR-C as a therapeutic approach for hypertension and cardiovascular disease prevention.|
|Rights:||Copyright © the authors, 2017. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.|
|Description:||Supplementary Material is available at HMG online. https://academic.oup.com/hmg/article-lookup/doi/10.1093/hmg/ddx375#supplementary-data|
|Appears in Collections:||Published Articles, Dept. of Cardiovascular Sciences|
Files in This Item:
|ddx375.pdf||Published (publisher PDF)||971.84 kB||Adobe PDF||View/Open|
Items in LRA are protected by copyright, with all rights reserved, unless otherwise indicated.