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

Abstract

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 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.

Obesity, starch digestion and amylase: association between copy number variants at human salivary (AMY1) and pancreatic (AMY2) amylase genes

“…( 13 ) and to the copy number gain defined by Cooke Bailey et al . ( 12 ). Detailed read-depth and long-PCR characterization of AMY2A deletions, corresponding approximately to CNVR266.9 of Conrad et al .…”

“…It is not clear why these views of AMY1 variation differ, and, in particular, whether the failure of real-time PCR studies to detect a preponderance of even numbers reveals a limitation of their accuracy, or whether the predominantly odd-numbered haplotypes observed in early studies represented a misleading sample. Furthermore, although most attention has focussed on AMY1 CNV, there have been reports of variation in copy number of the pancreatic AMY2A / 2B genes ( 3 , 7 , 12 , 13 ); however, the high-sequence identity between AMY1 and AMY2 genes makes resolving these CNVs unusually difficult, and these AMY2 variants, and their relationship to AMY1 variation, have not been clearly characterized.…”

Recurrent Rearrangements of Human Amylase Genes Create Multiple Independent CNV Series

“…Primarily because of its early discovery and extensive range, most attention on amylase CNVs has focussed on the salivary amylase gene AMY1 , but there have been reports of CNVs involving the AMY2 genes [Groot et al., ; Conrad et al., ; Sudmant et al., ; Cooke Bailey et al., ]. Integration of information from read‐depth analysis, segregation, and direct typing of copy number demonstrated haplotypes harboring even numbers of AMY1 in conjunction with CNVs of the pancreatic amylase genes AMY2A and AMY2B .…”

Genomic structural variations for cardiovascular and metabolic comorbidity

“…The leucine-rich repeat and Ig domain–containing 2 gene is expressed in neuronal tissue, and rs10968576 have been associated with body mass index3839. This study also revealed CNV at 1p21.1 affecting AMY2B gene known to be associated with type 2 diabetes mellitus40. The pancreatic alpha-amylase gene codes for a protein that catalyzes the initial step in digestion of dietary starch and glycogen.…”