Center for Translational Research in Health Disparities

健康差异转化研究中心

基本信息

批准号：
10221307
负责人：
Vincent C Bond
金额：
$ 17.75万
依托单位：
MOREHOUSE SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-07-07 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10221307
关键词：
2019-nCoV ACE2 Address Affect Africa African American American Bacteria Biology Blood specimen CCL2 gene COVID-19 COVID-19 diagnosis COVID-19 morbidity COVID-19 mortality COVID-19 patient COVID-19 severity COVID-19 treatment Caucasians Cells Center for Translational Science Activities Clinical Correlation Studies DNA Data Diabetes Mellitus Disease Disease Progression Female Frequencies Gene Expression Genes Genetic Genetic Predisposition to Disease Genetic Variation Genomics Goals HLA Antigens Health Heart Diseases Hospitals Hypertension Image Immune response Incidence Individual Institutes Integration Host Factors Knowledge Lung Lung diseases Minority Modeling Molecular Morbidity - disease rate Morehouse School of Medicine Not Hispanic or Latino Obesity Organoids Outcome Patients Peripheral Blood Mononuclear Cell Play Population Positioning Attribute Predisposition Progressive Disease Proteins Receptor Cell Research Risk Role SARS-CoV-2 infection Sampling Series Socioeconomic Factors Statistical Study Subgroup TMPRSS2 gene Testing Validation Variant Virus Work X Chromosome chemokine comorbidity cytokine differential expression disease disparity ezrin genetic variant health disparity health inequalities high risk machine learning algorithm male mortality novel outcome prediction predictive modeling racial disparity receptor transcriptome sequencing underserved minority

项目摘要

Abstract: Diversity in the rates of progression and mortality of COVID-19 disease within infected African American (AAs) subgroups are clearly not just a function of the underlying health conditions that increase the rate of mortality for COVID -19 patients, such as hypertension, obesity and diabetes, but may also be affected by host genetic factors. Here we propose a series of studies to advance the understanding of our knowledge in relative to the health inequity in COVID-19 disease. This is a multiple-collaborative study between Genomic, Imaging research labs and Statistical studies. Research teams in Morehouse School of Medicine (MSM) have established intimate relationships that position the institute to focus their research works on underserved minorities. We plan to develop and disseminate technological approaches in identifying host factors that disproportionately affect AAs COVID-19 infected patients. Given that the discovery, and establishment of translational implementation of novel solutions to health disparities in high-risk minority COVID-19 infected is our overall goals. Recently, angiotensin-converting enzyme 2 (ACE2), encoded on the X-chromosome, has been shown to be a functional receptor for COVID-19 to enter host target cells and the concern might arise regarding whether ACE2 variants between and within subgroups would increase the morbidity and mortality of COVID-19 infected patients. Therefore, the long-term goal is to compare how genetic variants of the ACE2 receptor, chemokine (CCL2) and human leukocyte antigen (HLA) genes (influence the immune system’s response to viruses and bacteria), affects COVID-19 disease severity among people but no underlining disease like diabetes, heart or lung disease with those with mild or no disease manifestations. Short-term goal; we will focus on two aims; Aim: 1-Determine genetic variations in ACE2 gene on obtained DNA samples from COVID-19 infected patients and evaluate for potential correlation between ACE2 variant frequencies in relationship to COVID-19 disease progression and mortalities between and within AAs and non-Hispanic Caucasian CAs subgroup;. COVID-19 is caused by SARS-CoV-2 which uses host cell ACE2, TMPRSS2, EZRIN and other proteins for entry. Differences in ACE2 or TMPRSS2/EZRIN genes expression and SNPs may justify the disease disparity and aim 2 will address how COVID-19 spike engagement with host cell receptor is precisely regulated and how host cells respond to cytokines elicited by COVID-19 infection using lung organoids. A recent correlation study suggested that the decrease expression of ACE2 /TMPRSS2/EZRIN are predictors of decreased susceptibility to COVID-19 infection and could be attributed to COVID-19 morbidity in Africa American patients. Aim-2: Modeling COVID-19-elicited disease disparity using lung organoids. Clinical validation of ACE2 and EZRIN will help to develop better strategies for COVID 19 diagnosis and treatment to reduce the observed COVID-19 disease progressive outcome and mortality gaps between African American and Caucasians patients. .

摘要：非洲感染者中 COVID-19 疾病的进展率和死亡率存在差异美国 (AA) 亚组显然不仅仅是增加潜在健康状况的函数 COVID-19患者的死亡率，如高血压、肥胖和糖尿病，也可能受到影响在这里，我们提出了一系列研究来加深对我们知识的理解。相对于 COVID-19 疾病的健康不平等，这是一项基因组、莫尔豪斯医学院 (MSM) 的影像研究实验室和统计研究团队拥有。建立了密切的关系，使研究所能够将研究工作重点放在服务不足的领域我们计划开发和传播技术方法来识别宿主因素，鉴于 AA 的发现和建立，对 COVID-19 感染患者的影响尤为严重。我们的目标是转化实施新的解决方案，解决高危少数群体感染 COVID-19 的健康差异问题最近，X 染色体上编码的血管紧张素转换酶 2 (ACE2) 已被确定。已被证明是 COVID-19 进入宿主靶细胞的功能性受体，因此可能会引起以下方面的担忧亚组之间和亚组内的 ACE2 变异是否会增加 COVID-19 的发病率和死亡率因此，长期目标是比较 ACE2 受体的遗传变异。趋化因子 (CCL2) 和人类白细胞抗原 (HLA) 基因（影响免疫系统对病毒和细菌），会影响人们的 COVID-19 疾病严重程度，但不会影响糖尿病等潜在疾病，患有轻度或无疾病表现的心脏或肺部疾病的人，我们将重点关注两个目标；目的；目的：1-确定从 COVID-19 获得的 DNA 样本中 ACE2 基因的遗传变异感染患者并评估 ACE2 变异频率之间的潜在相关性 AA 和非西班牙裔白种人之间以及内部的 COVID-19 疾病进展和死亡率 CAs 亚组；COVID-19 是由 SARS-CoV-2 引起的，它使用宿主细胞 ACE2、TMPRSS2、EZRIN 等 ACE2 或 TMPRSS2/EZRIN 基因表达和 SNP 的差异可能证明该疾病是合理的。差异和目标 2 将解决如何精确调节 COVID-19 尖峰与宿主细胞受体的结合以及宿主细胞如何利用肺类器官对 COVID-19 感染引起的细胞因子做出反应。研究表明 ACE2 /TMPRSS2/EZRIN 表达的减少是减少的预测因素非洲裔美国患者对 COVID-19 感染的易感性，可能归因于 COVID-19 发病。目标 2：使用肺类器官对 ACE2 和 ACE2 进行临床验证，对 COVID-19 引发的疾病差异进行建模。 EZRIN 将帮助制定更好的 COVID 19 诊断和治疗策略，以减少观察到的病例非裔美国人和白种人患者之间的 COVID-19 疾病进展结果和死亡率差异。。