The minor G allele of the SGK1 gene variant rs9402571 was associated with increased insulin secretion in lean non-diabetic individuals and a lower prevalence of type 2 diabetes (OR 0.85).
Observational (n=6,009)
Yes
Does the SGK1 rs9402571 minor G allele improve insulin secretion and reduce the prevalence of type 2 diabetes in European populations?
The SGK1 rs9402571 minor G allele is associated with increased insulin secretion in lean individuals and may confer a protective effect against type 2 diabetes.
Effect estimate: OR 0.85 (95% CI 0.71-1.01)
p-value: p=0.065
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.
Friedrich et al. (Wed,) conducted a observational in Type 2 Diabetes Mellitus (n=6,009). SGK1 gene variant rs9402571 minor G allele vs. Homozygous wild type TT carriers was evaluated on Prevalence of type 2 diabetes (METSIM cohort) (OR 0.85, 95% CI 0.71-1.01, p=0.065). The minor G allele of the SGK1 gene variant rs9402571 was associated with increased insulin secretion in lean non-diabetic individuals and a lower prevalence of type 2 diabetes (OR 0.85).