Dataset Information

Variance of the SGK1 gene is associated with insulin secretion in different European populations: results from the TUEF, EUGENE2, and METSIM studies.

ABSTRACT: HYPOTHESIS:Serum- and Glucocorticoid-inducible Kinase 1 (SGK1) is involved in the regulation of insulin secretion and may represent a candidate gene for the development of type 2 diabetes mellitus in humans. METHODS:Three independent European populations were analyzed for the association of SGK1 gene (SGK) variations and insulin secretion traits. The German TUEF project provided the screening population (N = 725), and four tagging SNPs (rs1763527, rs1743966, rs1057293, rs9402571) were investigated. EUGENE2 (N = 827) served as a replication cohort for the detected associations. Finally, the detected associations were validated in the METSIM study, providing 3798 non-diabetic and 659 diabetic (type 2) individuals. RESULTS:Carriers of the minor G allele in rs9402571 had significantly higher C-peptide levels in the 2 h OGTT (+10.8%, p = 0.04; dominant model) and higher AUC(C-Peptide)/AUC(Glc) ratios (+7.5%, p = 0.04) compared to homozygous wild type TT carriers in the screening population. As interaction analysis for BMIxrs9402571 was significant (p = 0.04) for the endpoint insulin secretion, we stratified the TUEF cohort for BMI, using a cut off point of BMI = 25. The effect on insulin secretion only remained significant in lean TUEF participants (BMI< or =25). This finding was replicated in lean EUGENE2 rs9402571 minor allele carriers, who had a significantly higher AUC(Ins)/AUC(Glc) (TT: 226+/-7, XG: 246+/-9; p = 0.019). Accordingly, the METSIM trial revealed a lower prevalence of type 2 diabetes (OR: 0.85; 95%CI: 0.71-1.01; p = 0.065, dominant model) in rs9402571 minor allele carriers. CONCLUSIONS:The rs9402571 SGK genotype associates with increased insulin secretion in lean non-diabetic TUEF/EUGENE2 participants and with lower diabetes prevalence in METSIM. Our study in three independent European populations supports the conclusion that SGK variability affects diabetes risk.

SUBMITTER: Friedrich B

PROVIDER: S-EPMC2575233 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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Variance of the SGK1 gene is associated with insulin secretion in different European populations: results from the TUEF, EUGENE2, and METSIM studies.

Friedrich Björn B Weyrich Peter P Stancáková Alena A Wang Jianjung J Kuusisto Johanna J Laakso Markku M Sesti Giorgio G Succurro Elena E Smith Ulf U Hansen Torben T Pedersen Oluf O Machicao Fausto F Schäfer Silke S Lang Florian F Risler Teut T Ullrich Susanne S Stefan Norbert N Fritsche Andreas A Häring Hans-Ulrich HU

PloS one 20081105 11

<h4>Hypothesis</h4>Serum- and Glucocorticoid-inducible Kinase 1 (SGK1) is involved in the regulation of insulin secretion and may represent a candidate gene for the development of type 2 diabetes mellitus in humans.<h4>Methods</h4>Three independent European populations were analyzed for the association of SGK1 gene (SGK) variations and insulin secretion traits. The German TUEF project provided the screening population (N = 725), and four tagging SNPs (rs1763527, rs1743966, rs1057293, rs9402571) ...[more]

PMID: 18985156

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Dataset Information

Variance of the SGK1 gene is associated with insulin secretion in different European populations: results from the TUEF, EUGENE2, and METSIM studies.

Publications

Variance of the SGK1 gene is associated with insulin secretion in different European populations: results from the TUEF, EUGENE2, and METSIM studies.

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