拷贝数变异在患有2型糖尿病相关终末期肾病的非裔美国人中的作用。

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

作者信息

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

机构信息

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.

Department of Biostatistical Sciences - Division of Public Health Sciences, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA.

出版信息

J Mol Genet Med. 2013 Jul 31;7:61. doi: 10.4172/1747-0862.1000061.

DOI:10.4172/1747-0862.1000061

PMID:24707315

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3973178/

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, OR=1.63) after multiple comparison correction. This CNV region encompasses the genes and , 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 CNV in T2D and/or T2D-ESRD, and indicate that CNVs may contribute to susceptibility for these diseases.

摘要

本研究调查了非裔美国人中2型糖尿病（T2D）及T2D相关终末期肾病（ESRD）与拷贝数变异（CNV）之间的关联。使用Affymetrix 6.0芯片，在965名患有T2D-ESRD的非裔美国人和1029名非糖尿病非裔美国人对照中，对跨越基因组的90多万个CNV探针进行了检测。对先前已鉴定的和新发现的CNV分别进行分析，并评估其插入/缺失状态，然后将其用作逻辑回归模型中的预测因子以检验关联性。经过多重比较校正后，1号染色体上一个常见的CNV插入与T2D-ESRD显著相关（p = 6.17×10，比值比= 1.63）。该CNV区域包含了和基因，它们编码由胰腺产生的淀粉酶同工酶。还检测到了其他一些与疾病接近显著相关的常见和新的CNV。这些探索性结果需要进一步验证，但提示了该CNV与T2D和/或T2D-ESRD有关，并表明CNV可能导致这些疾病的易感性。