Association of PI3K/AKT/mTOR Pathway Genetic Variants with Type 2 Diabetes Mellitus in Chinese

Aims: Genetic variations in the PI3K/AKT/mTOR signaling pathway may be associated with an increasing risk of obesity and diabetes. In this study, we aimed to test whether polymorphisms in the PIK3CA (catalytic subunit of PI3K), AKT1, AKT2, and FRAP1 (mTOR) genes were associated with the risk of type 2 diabetes mellitus (T2DM) among Chinese population.

Methods: A case-control study was conducted and included 248 cases with T2DM and 101 controls. A total of 28 tagSNPs from the 4 genes were chosen based on HapMap datasets and these were genotyped using a MassARRAY Compact Analyzer.

Results: Individuals carrying the rs2494746 CG/GG or rs2494738GA/GG genotype in AKT1 had a higher risk of T2DM, compared with those carrying homozygous variants (adjusted OR=1.79, 95% CI: 1.05-3.05, P=0.03 for rs2494746; adjusted OR=1.58, 95% CI: 1.19-2.10, P=0.02 for rs2494738). Furthermore, we found that haplotype GC in the AKT1 gene comprised rs2494738 and rs3803304, indicating a significant association with T2DM (OR=1.08, 95% CI: 1.01-1.15, P=0.03). Finally, generalized multifactor dimensionality reduction (GMDR) analysis indicated that the best interactive model included 3 polymorphisms: rs2494746 (AKT1), rs4802071 (AKT2), and rs4845856 (FRAP1).

Conclusions: Our study suggests that PI3K/AKT/mTOR pathway genes may participate in the development of T2DM.