Zaihan Zhu1, Yanfen Zhang1, Ruocen Bai1, Ru Yang1, Zhongyan Shan2, Chunyan Ma1, Jun Yang1, Dandan Sun1. 1. Department of Cardiovascular Ultrasound, The First Affiliated Hospital of China Medical University, Shenyang, China. 2. Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang, China.
Abstract
Introduction: MicroRNAs (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. Methods: Five 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. Results: In 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. Conclusion: MiRNAs 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.
Introduction: MicroRNAs (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-1rs13293512, miR-133a-1rs8089787, miR-133a-2rs13040413, and miR-27ars895819) and susceptibility to type 2 diabetes mellitus (T2DM), and its possible mechanisms. Methods: Five SNPs in miRNAs (let-7f rs10877887, let-7a-1rs13293512, miR-133a-1rs8089787, miR-133a-2rs13040413, and miR-27ars895819) 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. Results: In overall analyses, miR-133a-2rs13040413 and let-7a-1rs13293512 were related to the susceptibility to T2DM. In stratified analyses, miR-133a-2rs13040413, let-7a-1rs13293512 and miR-27ars895819 showed associations with T2DM in the age ≥ 60 years subgroup. Moreover, let-7a-1rs13293512 and miR-27ars895819 showed associations with T2DM in male subgroup. In SNP-environmental factors interaction analyses, there were interaction effects of miR-133a-2rs13040413 with dyslipidemia, let-7a-1rs13293512 with smoking, and let-7a-1rs13293512 with dyslipidemia on T2DM. In SNP-SNP interaction analyses, there were also interaction effects of miR-133a-1rs8089787 with let-7a-1rs13293512, and miR-133a-1rs8089787 with let-7f rs10877887 on T2DM. Furthermore, for miR-133a-2rs13040413, the variant T allele showed a trend toward decreased miR-133aexpression in comparison with the wild C allele. For let-7a-1rs13293512, the variant C allele expressed a lower let-7a compared to the wild T allele. Conclusion: MiRNAs 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.
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