The purpose of this study is to identify genes causing non- insulin- dependent diabetes mellitus (NIDDM)-associated nephropathy (NIDDM-NEPH) in high risk African American families. At most, 30 percent of diabetic patients are susceptible to nephropathy with it's invariable progression to end-stage renal disease (ESRD) and high mortality rate. African American and Native American populations are known to be at higher risk for developing NIDDM and it's associated Nephropathy, relative to whites. However, in all populations, select diabetic families demonstrate multi-generational clustering of renal disease. An inherited basis for NIDDM-NEPH is also supported by reports that racial differences in the prevalence and severity of diabetes mellitus and hypertension, socioeconomic status and access to health care fail to fully account for the excess risk of NIDDM-NEPH observed in African Americans, relative to whites. In order to identify genes causing NIDDM- NEPH we will continue to identify, clinically characterize, and collect DNA from NIDDM affected sibling pairs concordant and discordant for NIDDM-NEPH. This phase of the project employs the unique """"""""Family History of ESRD"""""""" database, independently compiled by the federally-funded ESRD Network 6 (Southeastern Kidney Council). This registry currently contains family history data from 7,600 incident patients with ESRD and contains data from more than 13,000 patients as of September, 1996 (60 percent of patients are African American; more than 35 percent have NIDDM-associated Nephropathy). Candidate genes will be screened for linkage to NIDDM-NEPH and a systematic genome wide survey for novel loci causing NIDDM-NEPH will be carried out. This effort will be formally linked to, and interact with, a parallel search for chromosome locations with evidence of linkage to insulin dependent diabetes associated nephropathy (IDDM-NEPH) in Caucasians through an interactive IRPG. The goal of this initial phase of the study is to locate chromosome regions with evidence of linkage to NIDDM-NEPH. The identification of NIDDM- NEPH genes would form a genetic basis for detection of high risk individuals and lead to development of intervention and treatment strategies for prevention of diabetic nephropathy, the most common etiology of ESRD in the U.S.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK053591-02
Application #
2906160
Study Section
Special Emphasis Panel (ZRG4-HPD (11))
Project Start
1998-09-30
Project End
2002-08-31
Budget Start
1999-09-01
Budget End
2000-08-31
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Biochemistry
Type
Schools of Medicine
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157
Guan, Meijian; Keaton, Jacob M; Dimitrov, Latchezar et al. (2018) An Exome-wide Association Study for Type 2 Diabetes-Attributed End-Stage Kidney Disease in African Americans. Kidney Int Rep 3:867-878
Keaton, Jacob M; Gao, Chuan; Guan, Meijian et al. (2018) Genome-wide interaction with the insulin secretion locus MTNR1B reveals CMIP as a novel type 2 diabetes susceptibility gene in African Americans. Genet Epidemiol 42:559-570
Gao, Chuan; Langefeld, Carl D; Ziegler, Julie T et al. (2018) Genome-Wide Study of Subcutaneous and Visceral Adipose Tissue Reveals Novel Sex-Specific Adiposity Loci in Mexican Americans. Obesity (Silver Spring) 26:202-212
Keaton, Jacob M; Hellwege, Jacklyn N; Ng, Maggie C Y et al. (2017) GENOME-WIDE INTERACTION WITH SELECTED TYPE 2 DIABETES LOCI REVEALS NOVEL LOCI FOR TYPE 2 DIABETES IN AFRICAN AMERICANS. Pac Symp Biocomput 22:242-253
Ma, Jun; Guan, Meijian; Bowden, Donald W et al. (2016) Association Analysis of the Cubilin (CUBN) and Megalin (LRP2) Genes with ESRD in African Americans. Clin J Am Soc Nephrol 11:1034-43
Williams, Robert C; Elston, Robert C; Kumar, Pankaj et al. (2016) Selecting SNPs informative for African, American Indian and European Ancestry: application to the Family Investigation of Nephropathy and Diabetes (FIND). BMC Genomics 17:325
Ma, Lijun; Langefeld, Carl D; Comeau, Mary E et al. (2016) APOL1 renal-risk genotypes associate with longer hemodialysis survival in prevalent nondiabetic African American patients with end-stage renal disease. Kidney Int 90:389-395
Guan, Meijian; Ma, Jun; Keaton, Jacob M et al. (2016) Association of kidney structure-related gene variants with type 2 diabetes-attributed end-stage kidney disease in African Americans. Hum Genet 135:1251-1262
Palmer, Nicholette D; Ng, Maggie C Y; Langefeld, Carl D et al. (2015) Lack of Association of the APOL1 G3 Haplotype in African Americans with ESRD. J Am Soc Nephrol 26:1021-5
Ng, Maggie C Y (2015) Genetics of Type 2 Diabetes in African Americans. Curr Diab Rep 15:74

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