Racial/Ethnic Disparities in Kidney Function Decline: Genes or Environment?

肾功能下降的种族/民族差异：基因还是环境？

• 批准号: 7570768
• 负责人: Carmen Alicia Peralta
• 金额: $ 16.08万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7570768
• 关键词: Address; Admixture; Adult; Adverse event; Affect; African; African American; Arts; Atherosclerosis; Award; Blood Pressure; Cardiovascular system; Caucasians; Caucasoid Race; Characteristics; Chinese American; Chronic Kidney Failure; Clinical; Complex; Creatinine; Data; Diabetes Mellitus; Disease Progression; Education; End stage renal failure; Environment; Environmental Risk Factor; Epidemic; Epidemiologist; Equation; Ethnic Origin; Ethnic group; Food; Foundations; Functional disorder; Future; Genes; Genetic; Genetic Predisposition to Disease; Genotype; Glomerular Filtration Rate; Goals; Hispanics; Incidence; Income; Individual; Intervention; Kidney; Kidney Diseases; Knowledge; Lead; Link; Low Prevalence; Low income; Maps; Measurement; Measures; Mentored Patient-Oriented Research Career Development Award; Mentors; Methods; Minority; Native Americans; Neighborhoods; Obesity; Participant; Pathway interactions; Patient Self-Report; Persons; Physical environment; Population; Prevention strategy; Psyche structure; Race; Relative (related person); Renal function; Research; Research Personnel; Resources; Risk; Risk Factors; Safety; Sample Size; Social Environment; Socioeconomic Factors; Socioeconomic Status; Staging; Subgroup; Testing; Time; Visit; Walking; Work; base; career development; cohesion; cohort; cost; disorder risk; gene environment interaction; genetic epidemiology; genome wide association study; high risk; improved; novel; novel marker; post gamma-globulins; programs; racial and ethnic; racial and ethnic disparities; social; social health determinants; socioeconomics; vascular inflammation

DESCRIPTION (provided by applicant): This is an application for a K23 award for Dr. Carmen A. Peralta, who proposes a novel, multi-disciplinary approach to understanding racial/ethnic disparities in kidney function decline. This award will allow Dr. Peralta the resources and protected time to achieve the following career development goals: (1) to become an independent, translational clinical researcher in the field of racial/ethnic disparities in kidney disease; (2) to become an expert in the application of genetic epidemiology methods to study these differences; and (3) to utilize sociodemographic measurements to improve understanding of the complex mechanisms involved in these disparities. To achieve these goals, Dr. Peralta has assembled a mentoring team comprised of her sponsor and primary mentor, Dr. Michael Shlipak (an expert in the field of cardiovascular complications of early kidney dysfunction), and two co-mentors: Dr. Neil Risch (a genetic epidemiologist) and Dr. Paula Braveman (an expert in social determinants of health). The epidemic of kidney disease currently affects 13% of U.S. adults, and the progression to end stage renal disease (ESRD) affects minorities disparately. African-Americans and Hispanics are the fastest growing groups in the ESRD population. Despite well-documented disparities in progression of advanced kidney disease to ESRD, no studies have evaluated the incidence of chronic kidney disease (CKD) or early kidney function decline in the US across racial/ethnic groups. It is unknown whether certain racial/ethnic groups have an increased genetic predisposition due to a common genetic ancestry or whether social or environ- mental factors explain observed differences. Using data from the Multi-Ethnic Study of Atherosclerosis (MESA), Dr. Peralta will compare rates of kidney function decline and incident CKD across four major racial groups and test possible genetic and sociodemographic mechanisms to explain these differences. Three specific aims are proposed: Aim 1: To compare rates of kidney function decline and incident chronic kidney disease across four major racial/ethnic groups (Caucasians, African-Americans, Hispanics, and Chinese- Americans) using creatinine and cystatin C based measures; Aim 2: To evaluate whether genetic ancestry is an independent predictor of kidney function decline and incident chronic kidney disease within racial groups and to explore gene-environment interactions in kidney function decline and incident kidney; and Aim 3: To evaluate the association of individual and neighborhood-level socioeconomic characteristics with kidney function decline and incident kidney disease across racial groups. Relevance: A better understanding of the mechanisms involved in racial/ethnic disparities in kidney function decline at earlier stages of kidney dysfunction could lead to important interventions and prevention strategies in halting this costly epidemic.

描述（由申请人提供）： 这是 Carmen A. Peralta 博士申请 K23 奖的申请，她提出了一种新颖的多学科方法来了解肾功能衰退中的种族/民族差异。该奖项将为 Peralta 博士提供资源和受保护的时间来实现以下职业发展目标：（1）成为肾脏疾病种族/民族差异领域的独立、转化型临床研究员； （2）成为应用遗传流行病学方法研究这些差异的专家； (3) 利用社会人口统计测量来增进对这些差异所涉及的复杂机制的理解。为了实现这些目标，Peralta 博士组建了一个指导团队，由她的资助者和主要导师 Michael Shlipak 博士（早期肾功能障碍心血管并发症领域的专家）和两位共同导师组成：Neil Risch 博士（遗传流行病学家）和 Paula Braveman 博士（健康问题社会决定因素专家）。目前，肾病的流行影响了 13% 的美国成年人，而终末期肾病 (ESRD) 的进展对少数群体的影响也不同。非裔美国人和西班牙裔美国人是 ESRD 人口中增长最快的群体。尽管晚期肾病进展为 ESRD 的差异有据可查，但尚无研究评估美国不同种族/族裔群体的慢性肾病 (CKD) 或早期肾功能衰退的发生率。目前尚不清楚某些种族/族裔群体是否由于共同的遗传血统而具有增加的遗传倾向，或者社会或环境因素是否解释了观察到的差异。 Peralta 博士将利用动脉粥样硬化多种族研究 (MESA) 的数据，比较四个主要种族群体的肾功能下降率和 CKD 发病率，并测试可能的遗传和社会人口学机制来解释这些差异。提出了三个具体目标： 目标 1：使用基于肌酐和胱抑素 C 的测量方法，比较四个主要种族/民族（白种人、非裔美国人、西班牙裔和华裔美国人）的肾功能下降率和慢性肾病发生率；目标 2：评估遗传血统是否是种族群体中肾功能衰退和慢性肾病发病的独立预测因素，并探索肾功能衰退和肾病发病中基因与环境的相互作用；目标 3：评估个人和社区层面的社会经济特征与不同种族群体肾功能下降和肾病发病率的关系。 相关性：更好地了解肾功能障碍早期阶段肾功能下降的种族/民族差异的机制可能会导致采取重要的干预措施和预防策略来阻止这种代价高昂的流行病。