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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