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

• 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
• 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

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.

项目摘要 多发性硬化症（MS）在美国影响大约一百万人，这是主要原因 年轻人的残疾，1但对其病因和潜在病理学知之甚少。2,3ms是 在女性中，女性的常见大约是男性的三倍，证据表明该比率是 在全球范围内增加。1-3尽管男性不太容易受到影响，但他们往往具有更严重的形式 疾病，因此更有可能积累严重的残疾。1-3证据表明 环境和性激素会导致分子变化改变MS相关的表达 基因，可以解释这些基于性别的疾病的欲望。1,2,6-12我们假设基因表达 改变会导致MS的性别差异。因此，此应用的目的是比较 使用以下两个特异性的男性和女性的转录组和miRNA谱。 目标。目标1：确定并比较男性转录组中主动表达的mRNA和 女性具有复发的MS和健康对照。为此，我们将进行非实验性， 基于发现的OMICS研究，该研究将分离和分析收集的血液样本的转录组 来自MS患者使用RNA-Seq。 AIM 2：分析男性和女性的miRNA特征 MS和健康对照。我们将使用纳米串来分析microRNA（miRNA）曲线并将其关联 mRNA水平可以更好地了解miRNA在MS疗法发生中的作用。 AIM 2B：探索 临床特征与RNA-seq和miRNA数据之间的关联。我们将探索关系 在显着差异表达的miRNA和mRNA谱和临床特征之间（MRI活性， CSF生物标志物和残疾）。这是第一个通过使用同质性的缩小MS表型的研究 人类样本以测量和比较MS中的基于性别的差异。这项研究的结果有望 阐明了MS表型，并在较大的同类人群中为未来的研究设计提供了信息 最终提高了该人群的护理质量。