Genetic variance of SGK-1 is associated with blood pressure, blood pressure change over time and strength of the insulin-diastolic blood pressure relationship

Wowern, Fredrik von; Berglund, G; Carlson, Joyce; Månsson, Henrik; Hedblad, Bo; Melander, Olle

doi:10.1111/j.1523-1755.2005.00672.x

Cited by 69 publications

(66 citation statements)

References 39 publications

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“…Genetic studies in twins indeed revealed a specific SGK1 risk haplotype associated with moderately elevated blood pressure in individuals who simultaneously carry a homozygous genotype for a variant in intron 6 (I6CC) and a homozygous or heterozygous genotype for the C allele of a polymorphism in exon 8 (E8CC/ CT) (81,82). This SGK1 risk haplotype was later confirmed to be associated with hypertension in a large-scale population study of Ͼ4800 Swedish subjects (83).…”

Section: Sgk1mentioning

confidence: 88%

Role of Epithelial Sodium Channels and Their Regulators in Hypertension

Soundararajan

Pearce

Hughey

et al. 2010

Journal of Biological Chemistry

104

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The kidney has a central role in the regulation of blood pressure, in large part through its role in the regulated reabsorption of filtered Na ؉ . Epithelial Na ؉ channels (ENaCs) are expressed in the most distal segments of the nephron and are a target of volume regulatory hormones. A variety of factors regulate ENaC activity, including several aldosterone-induced proteins that are present within an ENaC regulatory complex. Proteases also regulate ENaC by cleaving the channel and releasing intrinsic inhibitory tracts. Polymorphisms or mutations within channel subunits or regulatory pathways that enhance channel activity may contribute to an increase in blood pressure in individuals with essential hypertension.

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Section: Sgk1mentioning

confidence: 88%

Role of Epithelial Sodium Channels and Their Regulators in Hypertension

Soundararajan

Pearce

Hughey

et al. 2010

Journal of Biological Chemistry

104

View full text Add to dashboard Cite

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“…Moreover, moderately enhanced blood pressure values are observed in individuals carrying a variant of the SGK1 gene, affecting some 3-5% of unselected Caucasians [9,43]. Interestingly, the gene variant is associated with enhanced insulin sensitivity of blood pressure [43].…”

Section: Discussionmentioning

confidence: 99%

Lack of the serum and glucocorticoid-inducible kinase SGK1 attenuates the volume retention after treatment with the PPARγ agonist pioglitazone

Artunc

Sandulache

Nasir

et al. 2008

Pflugers Arch - Eur J Physiol

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PPARγ-agonists enhance insulin sensitivity and improve glucose utilization in diabetic patients. Adverse effects of PPARγ-agonists include volume retention and edema formation. Recent observations pointed to the ability of PPARγ agonists to enhance transcription of the serum and glucocorticoid-inducible kinase SGK1, a kinase that is genomically upregulated by mineralocorticoids and stimulates various renal channels and transporters including the renal epithelial Na + channel ENaC. SGK1 has been proposed to mediate the volume retention after treatment with PPARγ agonists. To test this hypothesis, food containing the PPARγ agonist pioglitazone (0.02%, i.e., approximately 25 mg/kg bw/day) was administered to gene-targeted mice lacking SGK1 (sgk1 −/− , n=12) and their wild-type littermates (sgk1 +/+ , n=12). According to in situ hybridization, quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and immunofluorescence, treatment with pioglitazone significantly increased renal SGK1 mRNA and protein expression in sgk1 +/+ mice. The treatment increased body weight significantly in both, sgk1 +/+ mice (+2.2±0.3 g) and sgk −/− mice (+1.3±0.2 g), and decreased hematocrit significantly in sgk1 +/+ mice (−6.5±1.0%) and sgk1 −/− mice (−3.1±0.6%). Both effects were significantly (p<0.05) more pronounced in sgk1 +/+ mice. According to Evans Blue

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“…The cornerstone of insulin resistance in the metabolic syndrome is a reduced sensitivity to the metabolic actions of insulin (3,4), initially leading to a compensatory increase in the levels of insulin to maintain glucose homeostasis. Indeed, recent findings suggest that raised levels of insulin in the metabolic syndrome stimulate the serumand glucocorticoid-regulated kinase 1 (SGK-1) in effect prolonging the half-life of the epithelial sodium channel which leads to sodium and water retention and raised levels of blood pressure (5).…”

Section: Introductionmentioning

confidence: 99%

Doubling of Water Intake Increases Daytime Blood Pressure and Reduces Vertigo in Healthy Subjects

Jormeus

Karlsson

Dahlgren

et al. 2010

Clinical and Experimental Hypertension

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We studied the effect of increased water intake on ambulatory BP in healthy individuals. BP was recorded after two weeks of either regular (RWI) or extra water intake (EWI, an additional 30 ml water/kg body weight per day) in 20 healthy subjects (10 males, 10 females).The extra water intake (RWI: 1.7 ± 0.59 l, EWI: 3.7 ± 0.84 l, respectively, p< 0.0001, i.e. an increase of 2 litres) induced an increase in mean arterial daytime BP from 89.0 ± 5.5 mmHg during RWI to 91.4 ± 6.4 mmHg during the EWI phase (p= 0.005) while night time BP was unchanged by the intervention. Visual-Analogue-Scale (VAS, maximum score of 10) score corresponding to the statement "I often experience vertigo" was 3.1 ± 2.6 during RWI and decreased to 2.1 ± 2. 1 during EWI phase (p= 0.008). In conclusion two litres of extra water intake for two weeks significantly increased daytime blood pressure and reduced sense of vertigo in healthy individuals.

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Genetic variance of SGK-1 is associated with blood pressure, blood pressure change over time and strength of the insulin-diastolic blood pressure relationship

Abstract: Our data suggest that SGK-1 risk carriers are at increased risk of hypertension and are more sensitive to the blood pressure elevating effects associated with hyperinsulinemia.

Cited by 69 publications

References 39 publications

Role of Epithelial Sodium Channels and Their Regulators in Hypertension

Role of Epithelial Sodium Channels and Their Regulators in Hypertension

Lack of the serum and glucocorticoid-inducible kinase SGK1 attenuates the volume retention after treatment with the PPARγ agonist pioglitazone

Doubling of Water Intake Increases Daytime Blood Pressure and Reduces Vertigo in Healthy Subjects

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