Exploring biomarkers of sex-based disparities in relapsing multiple sclerosis

项目摘要 多发性硬化症(MS)在美国影响着大约100万人，是主要原因 关于年轻人的残疾，1但对其病因和潜在的病理知之甚少。 女性的发病率大约是男性的三倍，有证据表明，这一比例是 1-3虽然男性不那么容易受到影响，但他们往往有更严重的形式的 疾病，因此更有可能积累严重的残疾。1-3证据表明， 环境和性激素可以引起分子变化，从而改变MS相关基因的表达 基因，这可能解释这些基于性别的疾病分离。1，2，6-12我们假设基因表达 因此，这个应用程序的目标是比较 男性和女性复发性多发性硬化症患者的转录组和miRNA图谱 目标。目的1：鉴定和比较男性和男性转录组中活跃表达的mRNAs 女性复发缓解型多发性硬化症患者和健康对照组。为此，我们将进行非试验性的， 基于发现的组学研究，将从采集的血液样本中分离和分析转录本 来自多发性硬化症患者使用RNA-seq.目的2：分析男性和女性复发者的miRNA图谱 多发性硬化和健康对照。我们将使用NanoString分析microRNA(MiRNA)图谱并将它们关联起来 以更好地了解miRNAs在MS发病机制中的作用。目标2b：探索 临床特征与rna-seq和miRNA数据的相关性。我们将探讨这一关系 显著差异表达的miRNA和信使核糖核酸图谱与临床特征(MRI活性， 脑脊液生物标志物和残疾)。这是第一次通过使用同源基因来缩小MS表型的研究 测量和比较多发性硬化症性别差异的人体样本这项研究的结果有望 阐明MS表型，并为未来在更大队列中进行的研究设计提供信息 最终提高这一人群的护理质量。

Project Summary Multiple Sclerosis (MS) affects approximately one million people in the United States and is the leading cause of disability in young adults,1 but little is known about its etiology and underlying pathology.2,3 MS is approximately three times more common in females than males, and evidence suggests that this ratio is increasing worldwide.1-3 Although males are less susceptible, they tend to have more severe forms of the disease, and are more likely to accumulate significant disability as a result.1-3 Evidence suggests that the environment and sex hormones can cause molecular changes that alter the expression of MS-associated genes, which may explain these sex-based disease desparities.1,2,6-12 We hypothesize that gene expression alterations contribute to the sex differences in MS. Therefore, the goal of this application is to compare the transcriptome and miRNA profiles of males and females with relapsing MS using the following two specific aims. Aim 1: Identify and compare the actively expressed mRNAs in the transcriptome of males and females with relapsing-remitting MS and healthy controls. For this aim we will conduct a non-experimental, discovery-based omics study that will isolate and analyze the transcriptomes from blood samples collected from MS patients using RNA-seq. Aim 2: Analyze the miRNA profiles of males and females with relapsing MS and healthy controls. We will analyze microRNA (miRNA) profiles using NanoString and correlate them with mRNA levels to better understand the role of miRNAs in MS etiopathogenesis. Aim 2b: Explore associations between clinical features and RNA-seq and miRNA data. We will explore the relationship between significantly differentially expressed miRNA and mRNA profiles and clinical features (MRI activity, CSF biomarkers, and disability).This is the first study to narrow the phenotype of MS by using homogeneous human samples to measure and compare sex-based differences in MS. Results of this study are expected to shed light on MS phenotypes, and to inform future study design in larger cohorts with the potential for ultimately improving the quality of care in this population.