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Title: The biological impact of blood pressure associated genetic variants in the natriuretic peptide receptor C gene on human vascular smooth muscle.
Authors: Ren, Meixia
Ng, Fu Liang
Warren, Helen R.
Witkowska, Kate
Baron, Michael
Jia, Zhilong
Cabrera, Claudia
Zhang, Ruoxin
Mifsud, Borbala
Munroe, Patricia B.
Xiao, Qingzhong
Townsend-Nicholson, Andrea
Hobbs, Adrian J.
Ye, Shu
Caulfield, Mark J.
First Published: 10-Oct-2017
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.
DOI Link: 10.1093/hmg/ddx375
ISSN: 0964-6906
eISSN: 1460-2083
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2017. This is an open-access article distributed under the terms of the Creative Commons Attribution License (, 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.
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

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