Sobhani Asma, InanlooRahatloo Kolsoum
School of Biology, College of Science, University of Tehran, Tehran, Iran.
Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
Cell J. 2024 Jul 13;26(5):320-328. doi: 10.22074/cellj.2024.2018050.1471.
The prevalence of neurological disorders often varies by sex, with conditions such as Alzheimer's disease and autism spectrum disorder (ASD) demonstrating notable differences in incidence. The aim of this study is to understand the molecular basis for these divergences in order to facilitate the creation of sex-specific therapeutic strategies.
This study is a bioinformatic analysis of publicly available RNA sequencing datasets involving autism patients. The study utilized RNA sequencing data from postmortem human brains' prefrontal cortex, including 38 neurotypical controls and 34 individuals with ASD. The sequencing data was obtained from previously published papers, and we downloaded the raw data from SRA. We investigated the molecular basis of sex-biased presentation in ASD through comprehensive transcriptomic analysis.
Comparative analysis of gene expression between male and female subjects, both autistic and unaffected, was conducted, using a significance level of ≤0.01. In autistic individuals, 136 genes demonstrated differential expression between sexes, predominantly upregulated in males, indicating a bias in male gene expression. Among these, 12 genes were identified as risk factors in the SFARI dataset. While most sex-biased genes were autosomal, expression differences on sex chromosomes were also observed in neurotypical subjects. Notable genes included TCF7L2, collagen family genes, and solute carrier family genes. In ASD males, extracellular matrix (ECM) organization emerged as a significant pathway, while immune-related processes were prominent in unaffected individuals.
Our study highlights the impact of the ECM pathway in ASD, with notable differences between sexes, particularly in males. shows promise as a potential biomarker for ASD in males. Recognizing the importance of sex differences in ASD transcriptomic research is crucial, as these variances provide insights into the disorder's pathophysiology and may guide the development of more personalized treatments for both sexes.
神经系统疾病的患病率常常因性别而异，诸如阿尔茨海默病和自闭症谱系障碍（ASD）等病症在发病率上表现出显著差异。本研究的目的是了解这些差异的分子基础，以便推动制定针对性别的治疗策略。
本研究是对公开可用的涉及自闭症患者的RNA测序数据集进行的生物信息学分析。该研究利用了来自人类死后大脑前额叶皮质的RNA测序数据，包括38名神经典型对照者和34名患有ASD的个体。测序数据取自先前发表的论文，我们从SRA下载了原始数据。我们通过全面的转录组分析研究了ASD中性别偏向表现的分子基础。
对自闭症和未受影响的男性与女性受试者之间的基因表达进行了比较分析，显著性水平设定为≤0.01。在自闭症个体中，有136个基因在性别之间表现出差异表达，主要在男性中上调，表明男性基因表达存在偏向。其中，有12个基因在SFARI数据集中被确定为风险因素。虽然大多数性别偏向基因是常染色体基因，但在神经典型受试者中也观察到了性染色体上的表达差异。值得注意的基因包括TCF7L2、胶原蛋白家族基因和溶质载体家族基因。在ASD男性中，细胞外基质（ECM）组织成为一个重要途径，而在未受影响的个体中免疫相关过程较为突出。
我们的研究突出了ECM途径在ASD中的影响，性别之间存在显著差异，尤其是在男性中。显示出作为男性ASD潜在生物标志物的前景。认识到ASD转录组研究中性别差异的重要性至关重要，因为这些差异为该疾病的病理生理学提供了见解，并可能指导为两性开发更个性化的治疗方法。
