Journal
HUMAN MOLECULAR GENETICS
Volume 27, Issue 1, Pages 199-210Publisher
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddx375
Keywords
-
Funding
- National Institute for Health Research (NIHR) Biomedical Research Unit in Cardiovascular Disease at Barts
- China Scholarship Council [2011632047]
- British Heart Foundation Clinical Fellowship [FS/12/82/29736]
- British Heart Foundation [PG/16/9/31995, RG/16/13/32609]
- Queen Mary, University of London
- MRC [MR/L016311/1, G0600237, G9521010] Funding Source: UKRI
- British Heart Foundation [PG/16/9/31995, PG/16/1/31892, TG/15/3/31692, PG/15/86/31723, PG/13/45/30326, PG/11/40/28891, FS/09/044/28007, RG/16/13/32609, FS/12/82/29736, SP/16/4/32697, PG/15/11/31279, RG/16/7/32357] Funding Source: researchfish
- Medical Research Council [G0600237, G9521010, MR/L016311/1, MC_qA137853, MR/K006584/1] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0512-10113, NF-SI-0617-10154] Funding Source: researchfish
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available