Functional Variants of miR-143 Are Associated with Schizophrenia Susceptibility: A Preliminary Population-Based Study and Bioinformatics Analysis,Biochemical Genetics

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Functional Variants of miR-143 Are Associated with Schizophrenia Susceptibility: A Preliminary Population-Based Study and Bioinformatics Analysis
Biochemical Genetics ( IF 2.1 ) Pub Date : 2021-09-13 , DOI: 10.1007/s10528-021-10133-z
Saman Sargazi ₁ , Fariba Mirani Sargazi ₁ , Milad Heidari Nia ₁ , Roghayeh Sheervalilou ₂ , Ramin Saravani _{1,

3} , Shekoufeh Mirinejad ₁ , Mansoor Shakiba ₄

Affiliation

Single nucleotide polymorphisms within genes encoding microRNAs may alter the expression of microRNAs and their target genes, contributing to the etiology of psychiatric disorders. We aimed to investigate the link between rs4705342T/C and rs4705343T/C polymorphisms in the promoter region of miR-143 and the risk of schizophrenia (SCZ) in a sample of an Iranian population. In this experimental study, a total of 398 subjects were recruited. Genotyping carried out using allele‐specific PCR (AS‐PCR) method. Different bioinformatics databases and Cytoscape V3.4.0 software were used for the analysis of the gene-miRNA interaction network. The genotypic analysis of rs4705342C/T showed that CC genotype in the co-dominant model significantly decreased the risk of SCZ (p < 0.001). Also, a significantly reduced risk of SCZ was observed under allelic (p < 0.001), dominant (p = 0.007), and recessive (p = 0.001) models of this variant. As regards rs4705343T/C, significantly enhanced risk of SCZ was found under the co-dominant CC (p = 0.01) and recessive (p = 0.007) contrasted genetic models. For this variant, the C allele conferred an increased risk of SCZ by 1.41 fold. Haplotype analysis showed that the C_rs4705342 T_rs4705343 haplotype significantly diminished SCZ susceptibility. The result of the bioinformatics analysis showed that miR-143, as a critical miRNA, targets ERK5, ERBB3, HK2, and PKCε, the four major genes involved in SCZ development. Our findings suggest that these two polymorphisms might affect SCZ susceptibility. Elucidating the precise regulatory mechanisms of gene expression in the development of SCZ will help researchers discover a novel target for therapeutic interventions.

Graphic Abstract

中文翻译：

miR-143 的功能变异与精神分裂症易感性相关：基于人群的初步研究和生物信息学分析

编码 microRNA 的基因中的单核苷酸多态性可能会改变 microRNA 及其靶基因的表达，从而导致精神疾病的病因。我们旨在调查miR-143启动子区域中 rs4705342T/C 和 rs4705343T/C 多态性与伊朗人群样本中精神分裂症 (SCZ) 风险之间的联系。在这项实验研究中，共招募了 398 名受试者。使用等位基因特异性PCR（AS-PCR）方法进行基因分型。使用不同的生物信息学数据库和Cytoscape V3.4.0软件对基因-miRNA相互作用网络进行分析。rs4705342C/T的基因型分析表明，共显性模型中CC基因型显着降低了SCZ的风险（p < 0.001)。此外，在该变体的等位基因 ( p < 0.001)、显性 ( p = 0.007) 和隐性 ( p = 0.001) 模型下观察到 SCZ 风险显着降低。至于rs4705343T/C，在显性CC（p = 0.01）和隐性（p = 0.007）对比遗传模型下发现SCZ的风险显着增加。对于这个变体，C 等位基因使 SCZ 的风险增加了 1.41 倍。单倍型分析表明，C _rs4705342 T _rs4705343单倍型显着降低了 SCZ 易感性。生物信息学分析结果表明，miR-143作为关键的miRNA，靶向ERK5、ERBB3、HK2和PKCε是参与 SCZ 发育的四个主要基因。我们的研究结果表明，这两种多态性可能会影响 SCZ 易感性。阐明 SCZ 发展过程中基因表达的精确调控机制将有助于研究人员发现治疗干预的新靶点。

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更新日期：2021-09-13

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