Clinical Trial: Mapping of End Stage Renal Disease Genetic Susceptibility in African Americans by Admixture Linkage Disequilibrium

Study Status: Completed
Recruit Status: Completed
Study Type: Observational

Official Title: Mapping of End Stage Renal Disease Genetic Susceptibility in African Americans by Admixture Linkage Disequilibrium

Brief Summary:

This study will identify which regions on the genes, and genes themselves, may account for an increased risk of end stage renal disease (ESRD), that is, near-total loss of kidney function, for people of African American descent. Researchers will use a technique called admixture linkage disequilibrium (MALD) to study genomes, genetic material, in about 2,500 participants from two existing studies and participants who will serve as controls. ESRD disproportionately affects African Americans, who constitute 29% of all ESRD patients in the Medicare ESRD program. The disease can result from a variety of diseases, with diabetes as the leading underlying cause (44% of cases) and hypertension as the second leading cause (26%). The proportion of ESRD cases caused by diabetes has increased dramatically.

Patients age 18 and older who are African American, who have ESRD, and who are participants of the FIND and CHOICE studies may be eligible for this study. FIND, or Family Investigation of Diabetes and Nephropathy, involves a multicenter study to identify susceptibility genes, that is, those with a risk, for diabetic and other forms of kidney disease. CHOICE, or Choices for Healthy Outcomes in Caring for ESRD patients is an ongoing study that identifies risk factors for cardiovascular outcomes in ESRD patients. The principle of mapping by MALD involves genetic variations that exist across populations. When mixing occurs between populations having different (heterogeneous) genes, the admixed offspring inherits chromosomes of distinct ancestry. However, over generations of mating, and recombination over several generations, originally large blocks of DNA from African ancestry have become part of smaller segments throughout the chromosome. The study will focus on risk alleles, that is, alternative forms of genes that carry a disease risk. Risk alleles are closely related to nearby ances

Detailed Summary:

Background:

• End stage renal disease (ESRD) is the near-total loss of kidney function which can result from a variety of diseases. ESRD disproportionately affects African Americans; this group comprises 29% of all ESRD patients treated in the Medicare ESRD program, a proportion that markedly exceeds their representation in the general population.
• The Family Investigation of Diabetes and Nephropathy (FIND) study is an ongoing study to identify susceptibility genes for diabetic and other forms of nephropathy, and the Choices for Healthy Outcomes in Caring for ESRD patients (CHOICE) study is an ongoing prospective study to identify risk factors for cardiovascular outcomes in ESRD patients. Participants of these studies have already been recruited and characterized with respect to renal phenotypes; furthermore, DNAs from these individuals have already been collected and isolated. In this study, we intend to genotype markers suitable for MALD analysis in African Americans. The central hypothesis of the present study is that some renal disease susceptibility alleles are present at higher frequency in African Americans than in whites and that specific regions of the genome in African Americans contain marker alleles that are in admixture linkage disequilibrium with ESRD susceptibility alleles.

Objectives:

• The overall objective of this study is to identify novel loci, genes, and gene products, that may partially account for excess risk of end stage renal disease (ESRD) in African Americans compared to whites.
• To achieve this goal, we will employ Mapping by Admixture Linkage Disequilibrium (MALD) analysis, a specialized form of linkage disequili
  Sponsor: National Cancer Institute (NCI)
  

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  Information By: National Institutes of Health Clinical Center (CC)
  

  Dates:
  Date Received: November 15, 2007
  Date Started: June 30, 2006
  Date Completion: April 10, 2012
  Last Updated: January 24, 2017
  Last Verified: April 10, 2012