Association of single nucleotide polymorphisms of miRNAs involved in the GLUT4 pathway in T2DM in a Chinese population.

BACKGROUND

The insulin/insulin receptor substrate (IRS)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/GLUT4 pathway plays a crucial role in insulin resistance and is closely associated with T2DM. Accumulating evidence indicates that miRNAs (such as miR-135a, let-7d, miR-107, miR-96, miR-29a, miR-23a, miR-126, miR-133a, and miR-106b) influence the GLUT4 pathway.

METHODS

A total of 784 subjects with T2DM and 846 nondiabetic subjects were enrolled and 12 single nucleotide polymorphisms (SNPs) in miRNAs (rs10459194 in miR-135a-2, rs10993081 and rs7045890 in let-7d, rs2296616 in miR-107, rs2402959 and rs6965643 in miR-96, rs24168 in miR-29a, rs3745453 in miR-23a, rs4636297 in miR-126, rs8089787 and rs9948906 in miR-133a-1 and rs999885 in miR-106b) involved in the GLUT4 pathway were genotyped using the MassArray method in a Chinese population.

RESULTS

Our data showed that the A allele of rs2402959 in miR-96 may increase the risk of developing T2DM (p = .002, OR = 1.266; 95% CI: 1.089-1.471). The genotypes of rs3745453 in miR-23a showed the difference between T2DM and control groups (p < .001). Moreover, for rs2402959, compared with the A/A genotype, the (G/A-G/G) genotype shows a protective effect in T2DM (p = .001, OR = 0.71; 95% CI: 0.58-0.87). For rs3745453, compared with the (A/A-A/G) genotype, the G/G genotype increases the risk of T2DM (p < .001, OR = 1.95; 95% CI: 1.38-2.77). In addition, we also found that rs4636297G/G genotype was associated with lower TC in T2DM group.

CONCLUSION

Our results revealed that genetic variations in the miRNAs involved in the GLUT4 pathway were associated with T2DM susceptibility in a Chinese population, and these results emphasize the need to study the functional effects of these variations in the miRNAs involved in the GLUT4 pathway on the risk of developing T2DM.