miR-146A和miR-146B启动子甲基化和共同序列变异不太可能参与自闭症谱系障碍

IF 2.7 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Sohair M. Salem, Nora N. Ismaiel, Ammal M. Metwally, Engy A. Ashaat, Maha M. Kobesiy
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引用次数: 0

摘要

其中一种被充分研究的表观遗传调控因子是miRNA (miRNA),它在基因调控中起着关键作用,并与自闭症谱系障碍(ASD)病理有关,特别是通过它们参与神经炎症和神经元调控。MiR-146A和miR-146B因其在ASD中的失调而受到特别关注。表观遗传修饰,如启动子甲基化和mirna的遗传变异可以影响它们的表达和功能,但它们在ASD中的作用尚不清楚。本研究旨在研究miR-146A和miR-146B的启动子甲基化模式和序列变化,以评估它们对ASD的潜在贡献。该研究纳入了使用DSM-V标准诊断并使用儿童自闭症评定量表(CARS)评估严重程度的埃及ASD患者(5-16岁)。从93名自闭症患者和44名年龄匹配的对照组的外周血样本中提取DNA。甲基化特异性PCR (MSP)用于分析miR-146A和miR-146B的启动子甲基化,而Sanger测序用于检测这些基因及其侧翼区域的序列变化。统计分析包括独立t检验、方差分析、ROC曲线和Pearson相关。在ASD病例和对照组之间以及严重程度亚组之间,miR-146A和miR-146B启动子甲基化水平无显著差异(P < 0.05)。序列变异分析发现,常见snp (rs2910164和rs2224374)的分布无显著差异。然而,在一个自闭症病例中发现了一种新的miR-146A上游变异(C/ a为5:16 0485254)。在这一人群中,miR-146A和miR-146B的甲基化和常见遗传变异不太可能在ASD中发挥重要作用。新的上游变异的发现凸显了调控区域在miRNA功能中的潜在重要性。建议进一步研究更大的队列和功能验证。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

miR-146A and miR-146B Promoter Methylation and Common Sequence Variations Are Not Likely to Be Involved in Autism Spectrum Disorder

miR-146A and miR-146B Promoter Methylation and Common Sequence Variations Are Not Likely to Be Involved in Autism Spectrum Disorder

One of the well-studied epigenetic regulators is miRNA (miRNA) which plays critical roles in gene regulation and has been implicated in autism spectrum disorder (ASD) pathology, particularly through their involvement in neuroinflammation and neuronal regulation. MiR-146A and miR-146B are of special interest due to their dysregulation in ASD. Epigenetic modifications, such as promoter methylation, and genetic variations in miRNAs can influence their expression and function, yet their roles in ASD remain unclear. This study aimed to investigate promoter methylation patterns and sequence variations in miR-146A and miR-146B to evaluate their potential contributions to ASD. The study included Egyptian patients with ASD (ages 5–16 years) diagnosed using DSM-V criteria and assessed for severity using the Childhood Autism Rating Scale (CARS). DNA was extracted from peripheral blood samples of 93 autistic patients and 44 age-matched controls. Methylation-specific PCR (MSP) was used to analyze promoter methylation of miR-146A and miR-146B, while Sanger sequencing was employed to detect sequence variations in these genes and their flanking regions. Statistical analyses included independent t-tests, ANOVA, ROC curve, and Pearson correlation. No significant differences in promoter methylation levels of miR-146A and miR-146B were observed between ASD cases and controls or among severity subgroups (P > 0.05). Sequence variation analysis identified no significant differences in the distribution of common SNPs (rs2910164 and rs2224374). However, a novel miR-146A upstream variant (C/A at 5:160,485,254) was discovered in one case with autism. Methylation and common genetic variations in miR-146A and miR-146B are unlikely to play significant roles in ASD in this population. The discovery of a novel upstream variant highlights the potential importance of regulatory regions in miRNA function. Further studies with larger cohorts and functional validation are recommended.

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来源期刊
Journal of Molecular Neuroscience
Journal of Molecular Neuroscience 医学-神经科学
CiteScore
6.60
自引率
3.20%
发文量
142
审稿时长
1 months
期刊介绍: The Journal of Molecular Neuroscience is committed to the rapid publication of original findings that increase our understanding of the molecular structure, function, and development of the nervous system. The criteria for acceptance of manuscripts will be scientific excellence, originality, and relevance to the field of molecular neuroscience. Manuscripts with clinical relevance are especially encouraged since the journal seeks to provide a means for accelerating the progression of basic research findings toward clinical utilization. All experiments described in the Journal of Molecular Neuroscience that involve the use of animal or human subjects must have been approved by the appropriate institutional review committee and conform to accepted ethical standards.
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