Medicina Molecular e Genética

The Role of Copy Number Variation in African Americans with Type 2 Diabetes-Associated End Stage Renal Disease

Abstract

Jessica N. Cooke Bailey, Lingyi Lu, Jeff W. Chou, Jianzhao Xu, David R. McWilliams, Timothy D. Howard, Barry I. Freedman, Donald W. Bowden, Carl D. Langefeld and Nicholette D. Palmer

This study investigated the association of copy number variants (CNVs) in type 2 diabetes (T2D) and T2Dassociated 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 genes AMY2A and AMY2B, 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 the AMY2A/AMY2B CNV in T2D and/or T2D-ESRD, and indicate that CNVs may contribute to susceptibility for these diseases.