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:10462322
- 负责人:
- 金额:$ 3.82万
- 依托单位:
- 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:
- 关键词:AddressAffectAgeAge of OnsetBiologicalBiological MarkersBlood specimenClinicalClinical Course of DiseaseDataDiseaseDisease ProgressionDisease stratificationDisease susceptibilityEmploymentEnvironmentEnvironmental Risk FactorEtiologyFemaleFinancial HardshipFutureGene ExpressionGene Expression AlterationGenesGenetic RiskGoalsGonadal Steroid HormonesHumanIn VitroKnowledgeLifeLightMagnetic Resonance ImagingMeasuresMessenger RNAMicroRNAsMolecularMultiple SclerosisNeurodegenerative DisordersNewly DiagnosedPathogenesisPathologyPathway interactionsPatientsPersonsPhenotypePopulationPreventive screeningPrognosisQuality of CareQuality of lifeRelapseRelapsing-Remitting Multiple SclerosisResearchResearch DesignResourcesRiskRoleSamplingSchool NursingSex DifferencesTechnologyTimeUnited Statesbasebiobehaviorcognitive disabilitycohortdifferential expressiondisabilitydisease disparitydisorder subtypegenetic variantgenome wide association studyimprovedimproved outcomein vivoindividual patientmalemolecular markermultiple sclerosis patientnano-stringneuropsychiatric disordernew therapeutic targetnext generationnovel markerpersonalized medicinephysically handicappedpsychologicsextranscriptometranscriptome sequencingtranscriptomicstreatment planningtreatment riskyoung 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.
项目摘要
多发性硬化症(MS)影响美国约一百万人,是主要原因
年轻人的残疾,1但对其病因学和潜在病理学知之甚少。2,3 MS是
在女性中大约是男性的三倍,有证据表明,这一比例是
1 -3虽然男性不太容易受到影响,但他们往往有更严重的形式,
疾病,并且更有可能因此累积严重残疾。1 -3证据表明,
环境和性激素可以引起分子变化,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绝望。1,2,6 -12我们假设,基因表达,
因此,本申请的目的是比较
使用以下两种特异性方法,
目标。目的1:鉴定和比较男性和女性转录组中活跃表达的mRNA,
复发缓解型MS女性患者和健康对照组。为此,我们将进行非实验性的,
一项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的MS患者。目的2:分析男性和女性复发性乳腺癌患者的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
与mRNA水平,以更好地了解在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
显著差异表达的miRNA和mRNA谱与临床特征(MRI活性,
这是第一个通过使用同质性的基因组标记来缩小MS表型的研究。
人类样本来测量和比较MS中基于性别的差异。本研究的结果预计将
阐明了MS表型,并为未来更大队列的研究设计提供信息,
最终提高这一人群的医疗质量。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Stephanie Kate Buxhoeveden其他文献
Stephanie Kate Buxhoeveden的其他文献
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{{ truncateString('Stephanie Kate Buxhoeveden', 18)}}的其他基金
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 - 财政年份:2022
- 资助金额:
$ 3.82万 - 项目类别:
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