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.
Keywords: Chinese population; GLUT4 pathway; T2DM; insulin resistance; microRNA; polymorphisms.
© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.