Low prevalence of nonconservative mutations of serum and glucocorticoid-regulated kinase (SGK1) gene in hypertensive and renal patients

Trochen, Nadja; Ganapathipillai, Santhirasekaran; Ferrari, Paolo; Frey, Brigitte M.; Frey, Felix J.

doi:10.1093/ndt/gfh417

Cited by 14 publications

(10 citation statements)

References 21 publications

(35 reference statements)

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“…A subsequent study on a similarly small group failed to observe an association of the same gene variant with blood pressure. 6 A most recent study in a very large group of individuals, however, clearly confirmed the association of the SGK1 gene variant with blood pressure and at the same time disclosed that the association was particularly prominent in individuals with hyperinsulinism. 7 This latter observation is in perfect agreement with recent observations in SGK1 knockout mice.…”

Section: Response: Clc-kb Mutation Revisitedmentioning

confidence: 86%

Activating Mutation of the Renal Epithelial Chloride Channel ClC-Kb Predisposing to Hypertension

Milton¹,

Jannes²,

Hamilton-Bruce³

et al. 2006

Hypertension

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Section: Response: Clc-kb Mutation Revisitedmentioning

confidence: 86%

Activating Mutation of the Renal Epithelial Chloride Channel ClC-Kb Predisposing to Hypertension

Milton¹,

Jannes²,

Hamilton-Bruce³

et al. 2006

Hypertension

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“…A subsequent study failed to detect a correlation of the gene variant with blood pressure in patients with renal failure [95]. The association between the gene variant and blood pressure was, however, later confirmed by a study in more than four thousand individuals [70].…”

Section: Discussionmentioning

confidence: 96%

Association of SGK1 Gene Polymorphisms with Type 2 Diabetes

Schwab

Lupescu²,

Moța

et al. 2008

Cell Physiol Biochem

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The serum and glucocorticoid inducible kinase SGK1 is genomically upregulated by glucocorticoids and in turn stimulates a variety of carriers and channels including the renal epithelial Na⁺ channel ENaC and the intestinal Na⁺ glucose transporter SGLT1. Twin studies disclosed an association of a specific SGK1 haplotype with moderately enhanced blood pressure in individuals who are carrying simultaneously 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] of the SGK1 gene. A subsequent study confirmed the impact of this risk haplotype on blood pressure. SGK1 knockout mice are resistant to the insulin and high salt induced increase of blood pressure, glucocorticoid induced increase of electrogenic glucose transport, and glucocorticoid induced suppression of insulin release. The present study explored whether the I6CC/E8CC/CT haplotype impacts on the prevalence of type 2 diabetes. The prevalence of the I6CC genotype was 3.1% in a healthy German, 2.4 % in a healthy Romanian and 11.6 % in a healthy African population from Ghana (p=0.0006 versus prevalence in Caucasians). Comparison of genotype frequencies between type 2 diabetic patients and the respective control groups revealed significant differences for the intron 6 T>C variant. Carriers of at least one T allele were protected against type 2 diabetes (Romanians: p=0.023; OR 0.29; 95% CI 0.09-0.89; Germans: p=0.01; OR 0.37; 95% CI 0.17-0.81). The SGK1 risk haplotype (I6CC/E8CC/CT) was significantly (p=0.032; OR 4.31, 95% CI 1.19-15.58) more frequent in diabetic patients (7.2 %) than in healthy volunteers from Romania (1.8%). The observations support the view that SGK-1 may participate in the pathogenesis of metabolic syndrome.

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“…In other contemporary studies, the subjects in the study by Busjahn et al [38] were monozygotic twins (n = 252, age 29 8 12 years) and dizygotic twins (n = 140, age 31 8 12 years) and in the study by Trochen et al [39] they were healthy normotensive individuals (n = 167, age 49 8 16 years) and hypertensive individuals (n = 113, age 59 8 17 years). It is possible that polymorphisms in SGK1 influence blood pressure only in certain age groups.…”

Section: Discussionmentioning

confidence: 99%

“…Trochen et al [39] investigated the same 2 polymorphisms, however, and concluded that they do not exert any significant effect on blood pressure in Caucasians. Our study showed that both rs1057293 and rs1743966 are associated with blood pressure in women in their 50s (n = 941; rs1057293: additive p = 0.034, dominant p = 0.0036; and rs1743966: dominant p = 0.036; data not shown).…”

Section: Discussionmentioning

confidence: 99%

Genetic Variations in the Sodium Balance-Regulating Genes ENaC, NEDD4L, NDFIP2 and USP2 Influence Blood Pressure and Hypertension

Jin

Hong

Lim

et al. 2010

Kidney Blood Press Res

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Background/Aims: In humans, the kidneys regulate blood pressure by balancing sodium concentrations. Fine-tuning of renal sodium reabsorption and excretion depends on the epithelial sodium channel protein (ENaC: protein complex of SCNN1A, SCNN1B, and SCNN1G). The surface expression of ENaC components is directed by the ubiquitination of ENaC by NEDD4L, an ENaC-specific E3 ubiquitin ligase, and is regulated by the deubiquitination of ENaC by USP2. The activity of NEDD4L in turn is regulated by phosphorylation by SGK1 and also through interaction with NDFIP2. Methods: We analyzed 91 SNPs in 7 genes using the genotype data of 8,842 individuals from the Korea Association REsource subject pool for their correlation with blood pressure and hypertension. Results: 25 SNPs in the SCNN1A, SCNN1B, SCNN1G, NEDD4L, NDFIP2, and USP2 loci were found to be associated with blood pressure. An additional hypertension case-control study identified 13 SNPs in SCNN1B, SCNN1G, and NEDD4L that were linked to hypertension. Conclusion: These results support our hypothesis that individual variations in blood pressure are attributed to variants of the genes that regulate renal sodium reabsorption and excretion. Our data also suggest that it would be meaningful to investigate the role of NEDD4L-mediated ubiquitination in the pathogenesis of hypertension.

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Low prevalence of nonconservative mutations of serum and glucocorticoid-regulated kinase (SGK1) gene in hypertensive and renal patients

Cited by 14 publications

References 21 publications

Activating Mutation of the Renal Epithelial Chloride Channel ClC-Kb Predisposing to Hypertension

Activating Mutation of the Renal Epithelial Chloride Channel ClC-Kb Predisposing to Hypertension

Association of SGK1 Gene Polymorphisms with Type 2 Diabetes

Genetic Variations in the Sodium Balance-Regulating Genes <i>ENaC</i>, <i>NEDD4L</i>, <i>NDFIP2</i> and <i>USP2</i> Influence Blood Pressure and Hypertension

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