Association of Genetic Polymorphisms in MicroRNAs With Type 2 Diabetes Mellitus in a Chinese Population.

Association of Genetic Polymorphisms in MicroRNAs With Type 2 Diabetes Mellitus in a Chinese Population.
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MicroRNA 基因多态性与中国人群 2 型糖尿病的关联

DOI:
10.3389/fendo.2020.587561
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发表时间:
2020
影响因子:
5.2
通讯作者:
Sun D
Sun D
中科院分区:
医学2区
文献类型:
--
作者:
Zhu Z;Zhang Y;Bai R;Yang R;Shan Z;Ma C;Yang J;Sun D

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参与胰岛素信号通路的MicroRNAs (miRNA)深入影响T2DM的发病机制。本研究的目的是评估相关miRNAs (let-7f rs10877887、let-7a-1 rs13293512、miR-133a-1 rs8089787、miR-133a-2 rs13040413和miR-27a rs895819)的单核苷酸多态性(SNP)与2型糖尿病(T2DM)易感性之间的关系及其可能的机制。方法在一项纳入371例T2DM患者和381例非糖尿病对照的病例对照研究中,选择参与胰岛素信号通路的mirna中的5个snp (let-7f rs10877887、let-7a-1 rs13293512、miR-133a-1 rs8089787、miR-133a-2 rs13040413和miR-27a rs895819)并进行基因分型。进行个体SNP关联分析、SNP-SNP互作分析、SNP-环境因子互作分析。我们还评估了风险相关多态性对其成熟miRNA表达的调控作用。结果在整体分析中,miR-133a-2 rs13040413和let-7a-1 rs13293512与T2DM易感性相关。在分层分析中,miR-133a-2 rs13040413、let-7a-1 rs13293512和miR-27a rs895819在年龄≥60岁亚组中显示与T2DM相关。此外,let-7a-1 rs13293512和miR-27a rs895819在男性亚组中显示与T2DM相关。在snp -环境因素互作分析中,miR-133a-2 rs13040413与血脂异常、let-7a-1 rs13293512与吸烟、let-7a-1 rs13293512与血脂异常对T2DM有互作作用。在SNP-SNP互作分析中,miR-133a-1 rs8089787与let-7a-1 rs13293512、miR-133a-1 rs8089787与let-7f rs10877887对T2DM也存在互作作用。此外,对于miR-133a-2 rs13040413,变异T等位基因与野生C等位基因相比,miR-133a表达有降低的趋势。对于let-7a-1 rs13293512,变体C等位基因表达的let-7a比野生T等位基因低。结论参与胰岛素信号通路的mirna多态性以及SNP-SNP、snp -环境因素的相互作用与中国人群T2DM易感性有关。
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.
DOI: 10.2337/diabetes.53.suppl_3.s34
发表时间: 2004-12-01
期刊: DIABETES
影响因子: 7.7
作者:
Chiasson, JL;Rabasa-Lhoret, M
通讯作者: Rabasa-Lhoret, M
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发表时间: 2014-04-04
影响因子: 4.8
作者:
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