The variant at TGFBRAP1 is significantly associated with type 2 diabetes mellitus and affects diabetes-related miRNA expression

Abstract

While the transforming growth factor-β1 (TGF-β1) regulates the growth and proliferation of pancreatic β-cells, its receptors trigger the activation of Smad network and subsequently induce the insulin resistance. A case-control was conducted to evaluate the associations of the polymorphisms of TGF-β1 receptor-associated protein 1 (TGFBRAP1) and TGF-β1 receptor 2 (TGFBR2) with type 2 diabetes mellitus (T2DM), and its genetic effects on diabetes-related miRNA expression. miRNA microarray chip was used to screen T2DM-related miRNA and 15 differential expressed miRNAs were further validated in 75 T2DM and 75 normal glucose tolerance (NGT). The variation of rs2241797 (T/C) at TGFBRAP1 showed significant association with T2DM in case-control study, and the OR (95% CI) of dominant model for cumulative effects was 1.204 (1.060-1.370), Bonferroni corrected P < 0.05. Significant differences in the fast glucose and HOMA-β indices were observed amongst the genotypes of rs2241797. The expression of has-miR-30b-5p and has-miR-93-5p was linearly increased across TT, TC, and CC genotypes of rs2241797 in NGT, P trend values were 0.024 and 0.016, respectively. Our findings suggest that genetic polymorphisms of TGFBRAP1 may contribute to the genetic susceptibility of T2DM by mediating diabetes-related miRNA expression.