Increased NBCn1 expression, Na+/HCO3− co-transport and intracellular pH in human vascular smooth muscle cells with a risk allele for hypertension. (13th January 2017)

• Record Type: Journal Article
• Authors: Ng, Fu Liang; Boedtkjer, Ebbe; Witkowska, Kate; Ren, Meixia; Zhang, Ruoxin; Tucker, Arthur; Aalkjær, Christian; Caulfield, Mark J.; Ye, Shu
• Is Part Of: Human molecular genetics. Volume 26:Number 5(2017:Mar. 01)
• Page Start: 989
• Page End: 1002
• Publication Date: 2017-01-13
• Subjects: Human molecular genetics -- Periodicals; Human chromosome abnormalities -- Periodicals; 572.8
• DOI: 10.1093/hmg/ddx015
• Languages: English
• ISSNs: 0964-6906

Abstract

Abstract: Genome-wide association studies have revealed an association between variation at the SLC4A7 locus and blood pressure. SLC4A7 encodes the electroneutral Na + /HCO 3 − co-transporter NBCn1 which regulates intracellular pH (pH i ). 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 pH i 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 pH i 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 pH i 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.