功能性miR-143/145聚类变异与2型糖尿病易感性的关系:初步病例对照研究和生物信息学分析

IF 1.5 4区 医学 Q4 ENDOCRINOLOGY & METABOLISM
Endocrine Research Pub Date : 2021-08-01 Epub Date: 2021-04-17 DOI:10.1080/07435800.2021.1914079
Danial Jahantigh, Fariba Mirani Sargazi, Saman Sargazi, Ramin Saravani, Saeedeh Ghazaey Zidanloo, Milad Heidari Nia, Maryam Piri
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引用次数: 18

摘要

目的:探讨miR-143/145簇启动子中两个变异(rs4705342和rs4705343)与2型糖尿病(T2DM)风险之间的联系。方法:采用ARMS-PCR方法对1200名受试者进行基因分型。结果:rs4705342变异增加了共显性CC下T2DM的风险(OR = 3.24;95% CI: 1.89-5.60),隐性TT+TC (OR = 3.02;95% CI: 1.77-5.17),显性TC+CC (OR = 1.35;95% CI: 1.08-1.71)遗传模型。携带rs4705342 C等位基因的个体患T2DM的风险增加1.43倍。至于rs4705343,共显性TC组T2DM风险降低(OR = 0.53;95% CI: 0.42-0.67),过显性TT+CC (OR = 0.51;95% CI: 0.40-0.64),显性TC+CC (OR = 0.59;95% CI: 0.48-0.75)模型。变异的单倍型分析显示,C - T组合使T2DM的风险增加1.941倍。T2DM患者不同单倍型与血脂指数之间存在显著相关性。调整BMI后p值无显著变化。计算分析显示,miR143和/或miR145靶向参与糖脂代谢的重要基因。结论:miR-143/145的功能变异可能影响T2DM的风险。因此,明确T2DM发病过程中基因表达的精确调控机制,将对研究人员寻找新的治疗干预靶点具有重要意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Relationship between Functional miR-143/145 Cluster Variants and Susceptibility to Type 2 Diabetes Mellitus: A Preliminary Case-Control Study and Bioinformatics Analyses.

Purpose: To investigate the link between two variants (rs4705342 and rs4705343) in the promoter of the miR-143/145 cluster with Type 2 diabetes mellitus (T2DM) risk. Methods:A total of 1200 subjects were genotyped using the ARMS-PCR method. Results: The rs4705342 variant enhanced the risk of T2DM under codominant CC (OR = 3.24; 95% CI: 1.89-5.60), recessive TT+TC (OR = 3.02; 95% CI: 1.77-5.17), and dominant TC+CC (OR = 1.35; 95% CI: 1.08-1.71) genetic models. Individuals carrying the C allele of rs4705342 conferred a 1.43 fold increased risk of T2DM. As regards rs4705343, decreased risk of T2DM was observed under codominant TC (OR = 0.53; 95% CI: 0.42-0.67), over-dominant TT+CC (OR = 0.51; 95% CI: 0.40-0.64), and dominant TC+CC (OR = 0.59; 95% CI: 0.48-0.75) models. Haplotype analysis of the variants showed a 1.941-fold increased risk of T2DM regarding the C T combination. Significant associations were noticed between different haplotypes and lipid indices of T2DM patients. There were no notable changes in p-values after adjustment for BMI. Computational analysis revealed that miR143 and/or miR145 target important genes involved in glucose and lipid metabolism. Conclusions: Functional miR-143/145 variants might influence the risk of T2DM. Hence, clarifying the precise regulatory mechanisms of gene expression in the development of T2DM will significantly guide researchers to find a novel target for therapeutic intervention.

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来源期刊
Endocrine Research
Endocrine Research 医学-内分泌学与代谢
CiteScore
4.30
自引率
0.00%
发文量
10
审稿时长
>12 weeks
期刊介绍: This journal publishes original articles relating to endocrinology in the broadest context. Subjects of interest include: receptors and mechanism of action of hormones, methodological advances in the detection and measurement of hormones; structure and chemical properties of hormones. Invitations to submit Brief Reviews are issued to specific authors by the Editors.
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