Original Paper

Association of SGK1 Gene Polymorphisms with Type 2 Diabetes
Matthias Schwab¹, Adrian Lupescu³, Maria Mota², Eugen Mota², Andreas Frey³, Perikles Simon⁴, Peter R. Mertens⁵, Jürgen Floege⁵, Friedrich Luft⁶, Steven Asante-Poku⁷, Elke Schaeffeler¹, Florian Lang<sup>3

1</sup>Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, and University of Tuebingen,
²University of Medicine and Pharmacy Craiova, Craiova,
³Depts. of Physiology and
⁴Sports Medicine, University of Tuebingen,
⁵Dept. of Nephrology, RWTH Aachen, and
⁶Dept. of Nephrology, University of Berlin;
⁷University of Ghana Medical School, Accra

Address of Corresponding Author

Cell Physiol Biochem 2008;21:151-160 (DOI: 10.1159/000113757)

  Key Words

• SGK1
• Type 2 diabetes
• Blood pressure
• Obesity
• Hypertension

  Abstract

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.

Copyright © 2008 S. Karger AG, Basel

  Author Contacts

Prof. Dr. Florian Lang
Department of Physiology, University of Tübingen
Gmelinstr. 5, D 72076 Tübingen (Germany)
Tel. + 49 7071 29 72194, Fax: + 49 7071 29 5618
E-Mail florian.lang@uni-tuebingen.de

  Article Information

Accepted: November 30, 2007
Published online: January 16, 2008
Number of Print Pages : 10