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

June 30, 2017 updated by: National Cancer Institute (NCI)

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 ancestral gene markers found in a person.

Patients will undergo a collection of blood and urine for genetic testing. Researchers are conducting separate analyses in this study. Case-control analysis of ESRD will consist of 1,150 participants from FIND and 250 from CHOICE. There will also be 750 control participants from FIND. For the case-control analysis of diabetic ESRD, there will be about 750 participants from FIND, 125 from CHOICE, and 750 controls from FIND. Finally, there is the quantitative trait analysis, which looks at the phenotype-meaning visible characteristics produced by the interaction of a person's genetic makeup with the environment. That analysis will involve 350 patients with diabetic nephropathy but not ESRD and 750 controls from FIND.

Study Overview

Status

Completed

Conditions

Detailed Description

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 disequilibrium mapping, to perform a genome-wide association study in approximately 2,500 African-American participants from the FIND and CHOICE studies.

Eligibility:

  • Specific Inclusion/Exclusion criteria: African American
  • Gender and minority inclusion. The FIND and CHOICE studies are open to both men and women of any ethnicity; however, due to the underlying principle of MALD analysis, this study will only include African-American participants of these cohorts.

Design:

  • Genotype 1536 African-American MALD markers (2 cM average spacing) utilizing DNA from approximately 2,500 African-American participants in FIND and CHOICE.

  • Perform a genome-wide association analysis utilizing a 2 cM dense genetic map and identify chromosomal loci that are in admixture linkage disequilibrium with:

    • ESRD in a case-control design
    • ESRD attributable to diabetes in a case-control design
    • Quantitative renal phenotypes
  • Fine map putative chromosomal region in admixture linkage disequilibrium with ESRD with densely-spaced single nucleotide polymorphisms.
  • A characterization of the MYH9 gene, its mRNA and the proteins encoded is planned for cases and controls. Gene sequencing of the region implicated will be undertaken. Characterization of mRNA products for quantities and alternative splicing will be evaluated. Experimental characterization of the MYH9 proteins for isoforms, post-translational modifications, interactions, and immunohistochemical staining will be performed.

Study Type

Observational

Enrollment (Anticipated)

2860

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Cancer Institute (NCI), 9000 Rockville Pike

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

  • INCLUSION CRITERIA:

The cohorts utilized in this study, FIND and CHOICE, are open to adults of both genders and any ethnicity. However, we will select and utilize only those samples from African - American participants. We will also utilize African (Yorban) and European controls for genotyping from the NIGMS HGCR.

EXCLUSION CRITERIA:

Children and all ethnicities other than African - American, African, and European will be excluded from this study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 30, 2006

Study Completion

April 10, 2012

Study Registration Dates

First Submitted

November 15, 2007

First Submitted That Met QC Criteria

November 15, 2007

First Posted (Estimate)

November 16, 2007

Study Record Updates

Last Update Posted (Actual)

July 2, 2017

Last Update Submitted That Met QC Criteria

June 30, 2017

Last Verified

April 10, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 999906210
  • 06-C-N210

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on End Stage Renal Disease (ESRD)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Egypt

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe