Serum- and glucocorticoid-regulated kinase (SGK1) gene and blood pressure.
The serum- and glucose-regulated kinase (SGK1) gene has recently been identified as an important aldosterone-induced protein kinase that mediates trafficking of the renal epithelial Na(+) channel (ENaC) to the cell membrane. Thus, SGK1 is an appealing candidate for blood pressure regulation and possibly essential hypertension. To test this hypothesis, we recruited monozygotic (126 pairs) and dizygotic (70 pairs) normotensive twin subjects and parents of dizygotic twins. Blood pressure was measured in a controlled fashion: recumbent, sitting, and upright. We documented genetic variance on blood pressure in all positions. We then relied on microsatellite markers at the SGK1 gene locus (D6S472, D6S1038, and D6S270) and 2 single nucleotide polymorphisms within the SGK1 gene. We found significant linkage of the SGK1 gene locus to diastolic blood pressure (P<0.0002) and suggestive evidence for linkage for systolic blood pressure (P<0.04), documenting the locus as a quantitative trait locus for blood pressure. We next performed association, using all dizygotic twins and a monozygotic member from each pair. We found significant associations between both single nucleotide polymorphism variants and blood pressure, as well as a significant interaction between the single nucleotide polymorphisms enhancing the effect. This combined effect of the polymorphisms was confirmed in an independent sample of 260 young normotensive men. We conclude that the SGK1 gene is relevant to blood pressure regulation and probably to hypertension in man.
Busjahn
Andreas
A
Franz Volhard Clinic, HELIOS Kliniken-Berlin and Max Delbrück Center for Molecular Medicine, Medical Faculty of the Charité, Humboldt University of Berlin, Germany.
Aydin
Atakan
A
Uhlmann
Regina
R
Krasko
Christine
C
Bähring
Sylvia
S
Szelestei
Tamas
T
Feng
Yuxi
Y
Dahm
Stephan
S
Sharma
Arya M
AM
Luft
Friedrich C
FC
Lang
Florian
F
D001794:Blood Pressure / Q000235:genetics*; D008040:Genetic Linkage; D014644:Genetic Variation; D006801:Humans; D006973:Hypertension / Q000235:genetics; D017874:Immediate-Early Proteins; D015810:Linkage Disequilibrium; D009687:Nuclear Proteins; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D019655:Quantitative Trait, Heritable; D020257:Ventricular Remodeling; D000099184:Serum-Glucocorticoid Regulated Kinases
D017874:Immediate-Early Proteins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D000099184:Serum-Glucocorticoid Regulated Kinases