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Family Investigation of Nephropathy of Diabetes (FIND) Consortium

Background

Variations in specific genomic regions have been associated with the differential prevalence of diabetic nephropathy and IgA nephropathy in certain populations. African- Americans, Hispanic-Americans, and Native Americans appear to have an increased incidence and prevalence of diabetic as well as non-diabetic renal disease.

In addition, recent findings have demonstrated that there is heterogeneity of renal histologic patterns in patients with type 2 diabetes mellitus and renal disease, although studies have shown a similarity of glomerular findings in patients with type 1 and type 2 diabetes mellitus and diabetic nephropathy. Such heterogeneity, as well as variations in response to different pharmacologic therapies, must be considered in planning studies of the genetic susceptibility to kidney disease in patients with diabetes mellitus. The differential susceptibility of the kidney to end-organ damage in different populations also suggests a role for genetic determinants in the pathogenesis of diabetic and non-diabetic renal diseases.

FIND Study Design

Because families of patients with diabetic nephropathy have an increased prevalence of renal disease and certain populations appear to be more susceptible, delineating the genetic loci associated with the development and progression of diabetic nephropathy could lead to improved outcomes. To accomplish this, the NIDDK and the National Center for Minority Health and Health Disparities have established the Family Investigation of Nephropathy of Diabetes (FIND) Consortium.

Recruitment for the independent studies got underway in August 2000. Recruitment goals are 2,000 pairs of siblings (1,180 affected and 743 discordant) for a family-based study, as well as approximately 1,500 cases and controls for an association study. The number of currently enrolled subjects is approximately 4,400. Participants will be of various ethnicities. Linkage analysis beginning with a genome scan will be performed. One part of the study is Mapping by Admixture Disequilibrium (MALD) in Mexican American and African American populations.

Eight investigator centers are conducting independent studies, using the facilities of a genetic analysis and data-coordinating center (GADCC). The centers are Case Western Reserve University; University of California, Los Angeles; Harbor-University of California Los Angeles Medical Center; University of Texas Health Science Center at San Antonio; Wake Forest University School of Medicine; Johns Hopkins University; University of New Mexico School of Medicine; and NIDDK/ Phoenix. The GADCC is located at Case Western Reserve University.

Recruitment for the independent studies got underway in August 2000. Recruitment goals are 2,000 pairs of siblings (1,180 affected and 743 discordant) for a family-based study, as well as approximately 1,500 cases and controls for an association study. The number of currently enrolled subjects is approximately 4,400.

In addition to conducting genetic and genomic studies, the FIND consortium is producing immortalized cell lines from all enrolled subjects and has established a database that uniformly and accurately collects genetic and phenotypic information reflecting underlying susceptibility to variable courses and outcomes of diabetic nephropathy. These resources will allow future researchers to re-analyze the samples and data from the FIND cohort. In 2001, research funds from the Type I diabetes initiative were used to add a diabetic retinopathy genetics component to the FIND study. The NIDDK and the National Eye Institute (NEI) jointly administer the retinopathy study.

The goal of the study is to evaluate whether there is a genetic link between diabetic nephropathy and diabetic retinopathy. Six of the eight clinical sites are participating in the retinopathy study. The Fundus Photograph Reading Center, located at University of Wisconsin, Madison, is funded to provide technical and training expertise for the participating clinical sites and to interpret all the clinical ophthalmologic data collected.

Eight investigator centers are conducting independent studies, using the facilities of a genetic analysis and data-coordinating center (GADCC). The centers are Case Western Reserve University; University of California, Los Angeles; Harbor-University of California Los Angeles Medical Center; University of Texas Health Science Center at San Antonio; Wake Forest University School of Medicine; Johns Hopkins University; University of New Mexico School of Medicine; and NIDDK/ Phoenix. The GADCC is located at Case Western Reserve University.

Investigational Approaches

Several strategies are available for identifying genomic regions involved in the pathogenesis of kidney disease and in the initiation and progression of diabetic retinopathy and nephropathy. Some involve genome scans and candidate gene analyses in family-based collections. Others are based on association studies with cases and controls. The FIND study will use the novel Mapping by Admixture Linkage Disequilibrium (MALD) analytic approach to study the case and control samples from the admixed Mexican-American and African-American populations.

Identification of gene sequences associated with susceptibility to the development or slow progression of diabetic nephropathy might provide markers for patients at risk for the development of ESRD, allow the early implementation of proved therapies, and provide rationales for the development of novel therapeutic strategies to treat renal disease. In addition, the elucidation of genetic susceptibility factors for retinopathy may help explain why these two diabetic complications have different risk factors.

Goals

The overall goal of FIND is to identify genetic pathways that may be critical for the development of nephropathy and lead to candidates amenable to therapeutic strategies to prevent the onset or progression of nephropathy. Such data might aid identification of people at risk for the development of progressive renal disease. The specific goals of this solicitation are as follows:

  • Facilitate the recruitment of representative patients and families with well-characterized renal diseases, especially the diabetic nephropathies
  • Delineate genomic regions associated with the development and progression of renal disease(s)
  • Evaluate whether there is a genetic link between diabetic nephropathy and diabetic retinopathy
  • Improve outcomes
  • Provide protection for people at risk and slow the progression of renal disease
  • Help establish a resource for genetic studies of kidney disease and diabetic complications by creating a repository of genetic samples and a database
  • Encourage studies of the genetics of progressive renal disease
NIDDK Program Officer: Dr. Rebekah Rasooly, 301-594-7717

Last Update: 4/13/2004


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