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

NCT00559767 | Completed

• 2 other identifiers: 99990621006-C-N210
• Study Type: observational
• Target: 2,860
• Locations: 1 country
• Sites: 1

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 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.

Conditions

End Stage Renal Disease (ESRD)

Keywords

Kidney Function; Genes; Association Analysis; Polymorphisms; Diabetes

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Cancer Institute (NCI), 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Patterson N, Hattangadi N, Lane B, Lohmueller KE, Hafler DA, Oksenberg JR, Hauser SL, Smith MW, O'Brien SJ, Altshuler D, Daly MJ, Reich D. Methods for high-density admixture mapping of disease genes. Am J Hum Genet. 2004 May;74(5):979-1000. doi: 10.1086/420871. Epub 2004 Apr 14.

  PMID: 15088269 BACKGROUND

• Smith MW, Patterson N, Lautenberger JA, Truelove AL, McDonald GJ, Waliszewska A, Kessing BD, Malasky MJ, Scafe C, Le E, De Jager PL, Mignault AA, Yi Z, De The G, Essex M, Sankale JL, Moore JH, Poku K, Phair JP, Goedert JJ, Vlahov D, Williams SM, Tishkoff SA, Winkler CA, De La Vega FM, Woodage T, Sninsky JJ, Hafler DA, Altshuler D, Gilbert DA, O'Brien SJ, Reich D. A high-density admixture map for disease gene discovery in african americans. Am J Hum Genet. 2004 May;74(5):1001-13. doi: 10.1086/420856. Epub 2004 Apr 14.

  PMID: 15088270 BACKGROUND

• Smith MW, Lautenberger JA, Shin HD, Chretien JP, Shrestha S, Gilbert DA, O'Brien SJ. Markers for mapping by admixture linkage disequilibrium in African American and Hispanic populations. Am J Hum Genet. 2001 Nov;69(5):1080-94. doi: 10.1086/323922.

  PMID: 11590548 BACKGROUND

MeSH Terms

Conditions

Kidney Failure, Chronic; Diabetes Mellitus

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Martha Linet, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Sponsor Type: NIH

Study Record Dates

• First Submitted: November 15, 2007
• First Posted: November 16, 2007
• Study Start: June 30, 2006
• Study Completion: April 10, 2012
• Last Updated: July 2, 2017

Record last verified: 2012-04-10

Locations

US (1)