Ancestry, Genetic Risk and Health Disparities in Immune-Mediated Nephritis

免疫介导性肾炎的血统、遗传风险和健康差异

基本信息

批准号：
9060186
负责人：
Andrew Stephen Bomback
金额：
$ 40万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-07-10 至 2019-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9060186
关键词：
Accounting African American Alleles Antigen-Antibody Complex Asians Autoantibodies Biological Markers Biopsy Biopsy Specimen Clinical Complex DNA Data Dialysis procedure Disease Disease Outcome End stage renal failure Environmental Risk Factor Ethnic Origin Ethnic group European Focal Segmental Glomerulosclerosis Functional disorder Future Gene Frequency Genetic Genetic Markers Genetic Risk Genotype Goals Health Hispanics IgA1 Immune Immunoglobulin A Individual Investigation Kidney Kidney Diseases Kidney Failure Lupus Lupus Nephritis Mediating Membranous Glomerulonephritis Minority Minority Groups Nephritis Outcome Paraffin Embedding Pathology Patient Self-Report Patients Phenotype Population Prevalence Recruitment Activity Renal function Renal glomerular disease Resources Risk Role Sampling Seminal Serum Severities Single Nucleotide Polymorphism Socioeconomic Factors Specimen Systemic Lupus Erythematosus Testing United States Variant base biobank cofactor cohort disease phenotype disorder subtype ethnic difference experience genetic association genetic risk factor genetic variant health disparity high risk non-diabetic novel therapeutic intervention racial and ethnic racial difference repository risk variant socioeconomics specific biomarkers

项目摘要

DESCRIPTION (provided by applicant): Immune-mediated glomerular disorders represent the third-most common cause of end-stage renal disease (ESRD), accounting for 14% of the dialysis population. IgA nephropathy (IgAN), membranous nephropathy (MN), and lupus nephritis (SLE-N) are the leading causes of primary and secondary immune-complex glomerular diseases. There are significant ethnic/racial differences in the prevalence and outcomes of these disorders. In particular, black and Hispanic patients are significantly more likely to progress to ESRD than whites across the spectrum of these glomerulopathies. These disparities are not solely attributable to environmental or socioeconomic factors. Recent studies, including from our group, have begun to delineate the contribution of genetic factors to variation in prevalence rates and renal outcomes in numerous glomerular diseases. The goal of this application is to systematically determine the degree to which genetic risk factors account for ethnicity-specific variation in prevalence, disease course, and overall outcomes of IgAN, MN, and SLE-N. In Aim 1, we will enrich our bio repository for specimens of glomerular disease patients with (a) preferential recruitment of black and Hispanic patients with IgAN, MN, and SLE-N and (b) DNA extraction from 3,000 anonymized kidney biopsy samples of these diseases. In Aim 2, we will use this bio repository to establish ethnicity-specific normative value for emerging biomarkers in IgAN, MN, and SLE-N that, to date, have primarily been tested in European and Asian populations. In Aim 3, we will incorporate genetic and biomarker data to better define differences in disease presentation and outcomes among ethnic/racial populations. We anticipate that there will be both distinct and shared genetic risk factors between both the subpopulations (Europeans, Asians, Hispanics, and African-Americans) and immune-mediated diseases under study. These findings will help identify individuals at high risk of IgAN, MN, and SLE-N; more precisely define the role of socio-economic and environmental cofactors in disease phenotypes; allow for discovery of new therapeutic interventions across the spectrum of immune-mediated diseases; and, finally, serve as an important resource for future investigations into the pathophysiology of these immune-mediated kidney diseases.

描述（由申请人提供）：免疫介导的肾小球疾病是终末期肾病 (ESRD) 的第三大常见原因，占透析人群的 14%。 IgA 肾病 (IgAN)、膜性肾病 (MN) 和狼疮性肾炎 (SLE-N) 是原发性和继发性免疫复合物肾小球疾病的主要原因。这些疾病的患病率和结果存在显着的种族差异。特别是，在这些肾小球疾病谱系中，黑人和西班牙裔患者进展为 ESRD 的可能性明显高于白人。这些差异不仅仅归因于环境或社会经济因素。最近的研究，包括我们小组的研究，已经开始描述遗传因素对多种肾小球疾病患病率和肾脏结果变化的影响。本应用的目标是系统地确定遗传风险因素对 IgAN、MN 和 SLE-N 患病率、病程和总体结果的种族特异性差异的程度。在目标 1 中，我们将通过 (a) 优先招募患有 IgAN、MN 和 SLE-N 的黑人和西班牙裔患者，以及 (b) 从这些患者的 3,000 个匿名肾活检样本中提取 DNA 来丰富肾小球疾病患者样本的生物存储库。疾病。在目标 2 中，我们将使用这个生物存储库为 IgAN、MN 和 SLE-N 中的新兴生物标志物建立种族特异性规范值，迄今为止，这些生物标志物主要在欧洲和亚洲人群中进行了测试。在目标 3 中，我们将整合遗传和生物标志物数据，以更好地定义种族/种族人群之间疾病表现和结果的差异。我们预计，所研究的亚人群（欧洲人、亚洲人、西班牙裔和非裔美国人）和免疫介导疾病之间将存在独特和共同的遗传风险因素。这些发现将有助于识别 IgAN、MN 和 SLE-N 高风险个体；更准确地定义社会经济和环境辅助因素在疾病表型中的作用；允许发现各种免疫介导疾病的新治疗干预措施；最后，作为未来研究这些免疫介导的肾脏疾病的病理生理学的重要资源。