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.
Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. adrao@partners.org
A D
AD
Rao
B
B
Sun
A
A
Saxena
P N
PN
Hopkins
X
X
Jeunemaitre
N J
NJ
Brown
G K
GK
Adler
J S
JS
Williams
D000328:Adult; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000235:genetics*; D016009:Chi-Square Distribution; D005060:Europe / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D017874:Immediate-Early Proteins / Q000235:genetics*; D016014:Linear Models; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage* / Q000009:adverse effects; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics; D000099184:Serum-Glucocorticoid Regulated Kinases
D015415:Biomarkers; D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D012083:Renin; D017673:Sodium Chloride, Dietary; D000099184:Serum-Glucocorticoid Regulated Kinases