Abstract
IntroductionMicroRNAs (miRNA) involved in the insulin signaling pathways deeply affect the pathogenesis of T2DM. The aim of this study was to assess the association between single nucleotide polymorphisms (SNP) of the related miRNAs (let-7f rs10877887, let-7a-1 rs13293512, miR-133a-1 rs8089787, miR-133a-2 rs13040413, and miR-27a rs895819) and susceptibility to type 2 diabetes mellitus (T2DM), and its possible mechanisms.MethodsFive SNPs in miRNAs (let-7f rs10877887, let-7a-1 rs13293512, miR-133a-1 rs8089787, miR-133a-2 rs13040413, and miR-27a rs895819) involved in the insulin signaling pathways were selected and genotyped in a case-control study that enrolled 371 T2DM patients and 381 non-diabetic controls. The individual SNP association analyses, interaction analyses of SNP-SNP, SNP-environmental factors were performed. The effect the risk-associated polymorphism on regulating its mature miRNA expression was also evaluated.ResultsIn overall analyses, miR-133a-2 rs13040413 and let-7a-1 rs13293512 were related to the susceptibility to T2DM. In stratified analyses, miR-133a-2 rs13040413, let-7a-1 rs13293512 and miR-27a rs895819 showed associations with T2DM in the age ≥ 60 years subgroup. Moreover, let-7a-1 rs13293512 and miR-27a rs895819 showed associations with T2DM in male subgroup. In SNP-environmental factors interaction analyses, there were interaction effects of miR-133a-2 rs13040413 with dyslipidemia, let-7a-1 rs13293512 with smoking, and let-7a-1 rs13293512 with dyslipidemia on T2DM. In SNP-SNP interaction analyses, there were also interaction effects of miR-133a-1 rs8089787 with let-7a-1 rs13293512, and miR-133a-1 rs8089787 with let-7f rs10877887 on T2DM. Furthermore, for miR-133a-2 rs13040413, the variant T allele showed a trend toward decreased miR-133a expression in comparison with the wild C allele. For let-7a-1 rs13293512, the variant C allele expressed a lower let-7a compared to the wild T allele.ConclusionMiRNAs polymorphisms involved in the insulin signaling pathways and the interaction effects of SNP-SNP, SNP-environmental factors were related to T2DM susceptibility in a Chinese population.
Highlights
MicroRNAs involved in the insulin signaling pathways deeply affect the pathogenesis of type 2 diabetes mellitus (T2DM)
The aim of this study was to assess the association between single nucleotide polymorphisms (SNP) of the related miRNAs and susceptibility to type 2 diabetes mellitus (T2DM), and its possible mechanisms
Increasing evidences have showed that various microRNAs involved in regulating the main protein cascades in the insulin signaling pathways that affect insulin resistance, and the pathogenesis of T2DM, such as let-7f with insulin growth factor-1 receptor (IGF1R), let-7a with phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT), miR-133a with glucose transporter 4 (GLUT4), and miR-27a with mammalian target of rapamycin [3,4,5,6]
Summary
MicroRNAs (miRNA) involved in the insulin signaling pathways deeply affect the pathogenesis of T2DM. Increasing evidences have showed that various microRNAs (miRNA) involved in regulating the main protein cascades in the insulin signaling pathways that affect insulin resistance, and the pathogenesis of T2DM, such as let-7f with insulin growth factor-1 receptor (IGF1R), let-7a with phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT), miR-133a with glucose transporter 4 (GLUT4), and miR-27a with mammalian target of rapamycin (mTOR) [3,4,5,6]. Blood level of let-7f was down-regulated in T2DM subjects compared to controls [7]. Let-7a overexpression could decrease the expression levels of PI3K and p-AKT [4]. Let-7f, let-7a, miR-133a, and miR27a have strong relationship with T2DM, both in underlying mechanisms and expression levels
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