Exploring biomarkers of sex-based disparities in relapsing multiple sclerosis

探索复发性多发性硬化症性别差异的生物标志物

基本信息

批准号：
10590599
负责人：
Stephanie Kate Buxhoeveden
金额：
$ 3.92万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-05-31 至 2024-05-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10590599
关键词：
Affect Age Age of Onset Biological Biological Markers Blood specimen Caring Clinical Clinical Course of Disease Data Disease Disease Progression Disease stratification Disease susceptibility Disparity Employment Environment Environmental Risk Factor Etiology Female Financial Hardship Future Gene Expression Gene Expression Alteration Genes Goals Gonadal Steroid Hormones Human In Vitro Knowledge Life Magnetic Resonance Imaging Measures Messenger RNA MicroRNAs Molecular Multiple Sclerosis Neurodegenerative Disorders Newly Diagnosed Pathogenesis Pathology Pathway interactions Patients Persons Phenotype Population Predisposition Preventive screening Prognosis Quality of Care Quality of life Relapse Relapsing-Remitting Multiple Sclerosis Research Research Design Resources Risk Role Sampling School Nursing Sex Differences Technology United States biobehavior cancer subtypes cognitive disability cohort differential expression disability disease disparity disorder subtype genetic risk factor genetic variant genome wide association study improved improved outcome in vivo individual patient male molecular marker multiple sclerosis patient nano-string neuropsychiatric disorder new therapeutic target next generation novel marker personalized medicine physically handicapped psychologic sex transcriptome transcriptome sequencing transcriptomics treatment planning treatment risk young adult

项目摘要

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.

项目概要多发性硬化症 (MS) 影响着美国大约一百万人，是主要原因年轻人的残疾，1 但对其病因和潜在病理学知之甚少。2,3 MS 是女性的发病率大约是男性的三倍，有证据表明这一比例全球范围内不断增加。1-3 尽管男性不太容易受到影响，但他们往往患有更严重的形式疾病，并且更有可能因此而积累严重的残疾。1-3 有证据表明，环境和性激素可引起分子变化，从而改变 MS 相关的表达基因，这可以解释这些基于性别的疾病差异。1,2,6-12 我们假设基因表达这些改变导致了多发性硬化症的性别差异。因此，本应用程序的目标是比较使用以下两个特定的方法对患有复发性多发性硬化症的男性和女性的转录组和 miRNA 谱进行分析目标。目标 1：鉴定并比较男性和女性转录组中活跃表达的 mRNA 患有复发缓解型多发性硬化症的女性和健康对照。为此，我们将进行一项非实验性的、基于发现的组学研究，将从收集的血液样本中分离和分析转录组使用 RNA-seq 从多发性硬化症患者中提取。目标 2：分析复发男性和女性的 miRNA 谱 MS 和健康对照。我们将使用 NanoString 分析 microRNA (miRNA) 谱并将它们关联起来通过 mRNA 水平更好地了解 miRNA 在 MS 发病机制中的作用。目标 2b：探索临床特征与 RNA-seq 和 miRNA 数据之间的关联。我们将探讨这种关系显着差异表达的 miRNA 和 mRNA 谱与临床特征（MRI 活性、 CSF 生物标志物和残疾）。这是第一项通过同质方法缩小 MS 表型的研究人类样本来测量和比较多发性硬化症的性别差异。这项研究的结果预计揭示 MS 表型，并为未来在更大队列中的研究设计提供信息，并有可能最终提高该人群的护理质量。