Ng, FL; Boedtkjer, E; Witkowska, K; Ren, M; Zhang, R; Tucker, A; Aalkjær, C; Caulfield, MJ; Ye, S
(2017)
Increased NBCn1 expression, Na+/HCO3- co-transport and intracellular pH in human vascular smooth muscle cells with a risk allele for hypertension.
Hum Mol Genet, 26 (5).
pp. 989-1002.
ISSN 1460-2083
https://doi.org/10.1093/hmg/ddx015
SGUL Authors: Ng, Fu Liang
Abstract
Genome-wide association studies have revealed an association between variation at the SLC4A7 locus and blood pressure. SLC4A7 encodes the electroneutral Na+/HCO3- co-transporter NBCn1 which regulates intracellular pH (pHi). We conducted a functional study of variants at this locus in primary cultures of vascular smooth muscle and endothelial cells. In both cell types, we found genotype-dependent differences for rs13082711 in DNA-nuclear protein interactions, where the risk allele is associated with increased SLC4A7 expression level, NBCn1 availability and function as reflected in elevated steady-state pHi and accelerated recovery from intracellular acidosis. However, in the presence of Na+/H+ exchange activity, the SLC4A7 genotypic effect on net base uptake and steady-state pHi persisted only in vascular smooth muscle cells but not endothelial cells. We found no discernable effect of the missense polymorphism resulting in the amino acid substitution Glu326Lys. The finding of a genotypic influence on SLC4A7 expression and pHi regulation in vascular smooth muscle cells provides an insight into the molecular mechanism underlying the association of variation at the SLC4A7 locus with blood pressure.
Item Type: |
Article
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Additional Information: |
© The Author 2017. Published by Oxford University Press.
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 reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: |
Alleles, Amino Acid Substitution, Animals, Blood Pressure, DNA-Binding Proteins, Endothelial Cells, Gene Expression Regulation, Genome-Wide Association Study, Genotype, Humans, Hydrogen-Ion Concentration, Hypertension, Muscle, Smooth, Vascular, Mutation, Rats, Sodium, Sodium-Bicarbonate Symporters, Muscle, Smooth, Vascular, Endothelial Cells, Animals, Humans, Rats, Hypertension, Sodium, Sodium-Bicarbonate Symporters, DNA-Binding Proteins, Amino Acid Substitution, Gene Expression Regulation, Blood Pressure, Genotype, Mutation, Alleles, Hydrogen-Ion Concentration, Genome-Wide Association Study, Genetics & Heredity, 06 Biological Sciences, 11 Medical and Health Sciences |
SGUL Research Institute / Research Centre: |
Academic Structure > Institute of Medical & Biomedical Education (IMBE) |
Journal or Publication Title: |
Hum Mol Genet |
ISSN: |
1460-2083 |
Language: |
eng |
Dates: |
Date | Event |
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1 March 2017 | Published | 13 January 2017 | Published Online | 30 December 2016 | Accepted |
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Publisher License: |
Creative Commons: Attribution 4.0 |
Projects: |
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PubMed ID: |
28087731 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/112397 |
Publisher's version: |
https://doi.org/10.1093/hmg/ddx015 |
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