APOL1, sickle cell trait and chronic kidney disease in African Americans

APOL1、镰状细胞特征和非裔美国人的慢性肾病

基本信息

批准号：
9337929
负责人：
Nora Franceschini
金额：
$ 30万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-16 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9337929
关键词：
Accounting Address Africa African African American Albumins Alleles Atherosclerosis Behavioral Biological Markers Blood Vessels Cardiovascular Diseases Caring Case-Control Studies Cessation of life Chronic Kidney Failure Clinical Collaborations Comorbidity Coronary heart disease Creatinine Data Data Set Development Diabetes Mellitus Disease Outcome Disease Progression Dyslipidemias End stage renal failure Environmental Risk Factor Event Fetal Hemoglobin Functional disorder Genes Genetic Genomics Genotype Goals Health Healthcare Hemoglobin concentration result High Density Lipoprotein Cholesterol High Density Lipoproteins Hypertension Individual Inflammation Inflammatory Information Systems Ischemic Stroke Jackson Heart Study Kidney Kidney Diseases Knowledge Malaria Measurement Measures Mediating Medical Genetics Missense Mutation Mission National Institute of Diabetes and Digestive and Kidney Diseases Natural Immunity Participant Penetrance Phenotype Pilot Projects Population Predisposition Prevention Public Health Research Resistance Resources Risk Risk Estimate Risk Factors Role Serum Severities Sickle Cell Anemia Sickle Cell Trait Sickle Hemoglobin Sleep Stroke Thalassemia Thrombosis Urine Variant Woman Women&apos s Health admixture mapping base beta Globin biobank burden of illness cardiovascular disorder risk cardiovascular risk factor cholesterol-binding protein clinical care cohort cost effective disorder risk economic cost endothelial dysfunction follow-up genetic risk factor genetic variant genome wide association study genome-wide health disparity high risk innovation insight lipid metabolism mortality novel pathogen population based risk variant socioeconomics

项目摘要

Pilot study of African-specific variants and chronic kidney disease The over-arching goal of this pilot study is to provide additional data to support a larger R01 application that defines new directions for the roles of African-specific risk alleles (APOL1 and the sickle cell trait [SCT] rs334 variant), and novel genetic and environmental modifiers of APOL1 and SCT, on risk of chronic kidney disease and end-stage renal disease in African Americans. Our main goal is to better understand the clinically observed varying kidney disease risk and progression in African Americans carrying these high risk genotypes. Chronic kidney disease is a devastating condition associated with substantial cardiovascular disease burden, and socio-economic cost. APOL1 risk alleles confer 5- to 29-fold increased risk to end-stage renal disease in case-control studies, but only a 2-fold risk to chronic kidney disease in population studies. The role of SCT in progression to end-stage renal disease remains unclear. Our research hypothesis is that as yet unidentified genetic and environmental factors explain the variable clinical penetrance of chronic kidney disease in individuals with these risk alleles. Leveraging the existing, but untapped biorepository resource of the largest population-based longitudinal data set of African Americans in the U.S., we will perform baseline serum creatinine measurements in 3,826 African American women from the Women’s Health Initiative, to allow an unprecedented examination of the risk and progression of chronic kidney disease associated with APOL1 and SCT in African Americans.

非洲特有变异和慢性肾脏病的试点研究这项试点研究的首要目标是提供额外的数据来支持更大的 R01 应用，该应用定义了非洲特有风险等位基因（APOL1 和镰状细胞性状 [SCT] rs334 变体）和新遗传基因作用的新方向。 APOL1 和 SCT 的环境调节剂对非裔美国人慢性肾病和终末期肾病的风险的影响我们的主要目标是更好地了解携带这些高风险的非裔美国人中临床观察到的不同肾病风险和进展。慢性肾病是一种毁灭性的疾病，与大量的心血管疾病负担相关，在病例对照研究中，APOL1 风险等位基因使终末期肾病的风险增加 5 至 29 倍，但仅增加 2 倍。在人群研究中，SCT 在进展为终末期肾病中的作用仍不清楚，但尚未确定的遗传和环境因素可以解释慢性肾病患者临床外显率的差异。这些风险利用美国最大的非裔美国人人口纵向数据集现有但尚未开发的生物存储资源，我们将对妇女健康倡议的 3,826 名非裔美国女性进行基线血清肌酐测量，以便对风险进行前所未有的检查以及非裔美国人中与 APOL1 和 SCT 相关的慢性肾脏疾病的进展。