The Role of Copy Number Variation in African Americans with Type 2 Diabetes-Associated End Stage Renal Disease.
This study investigated the association of copy number variants (CNVs) in type 2 diabetes (T2D) and T2D-associated end-stage renal disease (ESRD) in African Americans. Using the Affymetrix 6.0 array, >900,000 CNV probes spanning the genome were interrogated in 965 African Americans with T2D-ESRD and 1029 non-diabetic African American controls. Previously identified and novel CNVs were separately analyzed and were evaluated for insertion/deletion status and then used as predictors in a logistic regression model to test for association. One common CNV insertion on chromosome 1 was significantly associated with T2D-ESRD (p=6.17×10-5, OR=1.63) after multiple comparison correction. This CNV region encompasses the genesAMY2AandAMY2B, which encode amylase isoenzymes produced by the pancreas. Additional common and novel CNVs approaching significance with disease were also detected. These exploratory results require further replication but suggest the involvement of theAMY2A/AMY2BCNV in T2D and/or T2D-ESRD, and indicate that CNVs may contribute to susceptibility for these diseases.
Program in Molecular Medicine and Translational Science, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA ; Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA ; Center for Diabetes Research, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA.
Jessica N Cooke
JN
Bailey
Department of Biostatistical Sciences - Division of Public Health Sciences, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA.
Lingyi
L
Lu
Department of Biostatistical Sciences - Division of Public Health Sciences, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA.
Jeff W
JW
Chou
Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA.
Jianzhao
J
Xu
Department of Biostatistical Sciences - Division of Public Health Sciences, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA.
David R
DR
McWilliams
Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA.
Timothy D
TD
Howard
Department of Internal Medicine - Section on Nephrology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA.
Barry I
BI
Freedman
Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA ; Center for Diabetes Research, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA ; Department of Biochemistry, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA ; Department of Internal Medicine - Section on Endocrinology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA.
Donald W
DW
Bowden
Department of Biostatistical Sciences - Division of Public Health Sciences, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA.
Carl D
CD
Langefeld
Program in Molecular Medicine and Translational Science, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA ; Center for Diabetes Research, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA ; Department of Biochemistry, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA.
Nicholette D
ND
Palmer
African Americans; Copy number variation; Diabetic nephropathy; End-stage renal disease; Genome-wide association study; Type 2 diabetes