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Polymorphisms in the serum- and glucocorticoid-inducible kinase 1 gene are associated with blood pressure and renin response to dietary salt intake


Serum- and glucocorticoid-inducible kinase 1 (SGK1) has a central role in epithelial sodium channel (ENaC)-dependent Na+ transport in the distal nephron. We hypothesized that SGK1 gene variants may contribute to the effect of dietary salt intake on blood pressure (BP) in humans with hypertension, and consequentially influence renin–angiotensin–aldosterone (RAA) system activity. Our study population included 421 hypertensive Caucasian participants of the HyperPath group who had completed a dietary salt protocol with measurement of BP and RAA system activity. Three SGK1 tagging single nucleotide polymorphisms (SNPs) from the HapMap CEU population captured the genetic variation in the SGK1 region. Assuming an additive genetic model, two SNPs (rs2758151 and rs9402571) were associated with BP and plasma renin activity (PRA) effects of dietary salt intake. Major alleles were associated with higher systolic BP on high salt and decreased PRA on low salt. In contrast, low salt neutralized genotype differences. Similar, non-significant trends were observed in a normotensive population (N=152). Genotype was also associated with two salt-sensitive subtypes of hypertension. SGK1 genetic variants are associated with salt sensitivity of BP and PRA in human hypertension. Genotype status at these SGK1 variants may identify individuals prone to salt-sensitive hypertension.

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We would like to thank the staff of the clinical research centers at our collaborating institutions and the volunteers of this study. This project was supported in part by the following grants: U54LM008748, from the National Library of Medicine; UL1RR025758 Harvard Clinical and Translational Science Center; M01RR02634, M01RR00095, M01RR00064, from the National Center for Research Resources as well as NIH grants HL47651, HL59424, K23HL084236 (JSW), K24HL103845 (GKA) and the Specialized Center of Research (SCOR) in Molecular Genetics of Hypertension P50HL055000. ADR was supported by a NIH training grant (T32 HL007609).

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Correspondence to A D Rao.

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Rao, A., Sun, B., Saxena, A. et al. Polymorphisms in the serum- and glucocorticoid-inducible kinase 1 gene are associated with blood pressure and renin response to dietary salt intake. J Hum Hypertens 27, 176–180 (2013).

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