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Diabetes. 2014 Jul;63(7):2506-15. doi: 10.2337/db13-1716. Epub 2014 Mar 4.

Risk of type 1 diabetes progression in islet autoantibody-positive children can be further stratified using expression patterns of multiple genes implicated in peripheral blood lymphocyte activation and function.

Author information

1
Sino-American Institute of Translational Medicine, School of Pharmaceutical Sciences, Nanjing University of Technology, Nanjing, ChinaCenter for Biotechnology and Genomic Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GADepartment of Pathology, Medical College of Georgia, Georgia Regents University, Augusta, GA.
2
Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GADepartment of Pathology, Medical College of Georgia, Georgia Regents University, Augusta, GA.
3
Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GA.
4
Sino-American Institute of Translational Medicine, School of Pharmaceutical Sciences, Nanjing University of Technology, Nanjing, ChinaCenter for Biotechnology and Genomic Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GA.
5
Barbara Davis Center for Childhood Diabetes, Aurora, CO.
6
Barbara Davis Center for Childhood Diabetes, Aurora, CO jshe@gru.edu marian.rewers@ucdenver.edu.
7
Sino-American Institute of Translational Medicine, School of Pharmaceutical Sciences, Nanjing University of Technology, Nanjing, ChinaCenter for Biotechnology and Genomic Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GADepartment of Pathology, Medical College of Georgia, Georgia Regents University, Augusta, GA jshe@gru.edu marian.rewers@ucdenver.edu.

Abstract

There is tremendous scientific and clinical value to further improving the predictive power of autoantibodies because autoantibody-positive (AbP) children have heterogeneous rates of progression to clinical diabetes. This study explored the potential of gene expression profiles as biomarkers for risk stratification among 104 AbP subjects from the Diabetes Autoimmunity Study in the Young (DAISY) using a discovery data set based on microarray and a validation data set based on real-time RT-PCR. The microarray data identified 454 candidate genes with expression levels associated with various type 1 diabetes (T1D) progression rates. RT-PCR analyses of the top-27 candidate genes confirmed 5 genes (BACH2, IGLL3, EIF3A, CDC20, and TXNDC5) associated with differential progression and implicated in lymphocyte activation and function. Multivariate analyses of these five genes in the discovery and validation data sets identified and confirmed four multigene models (BI, ICE, BICE, and BITE, with each letter representing a gene) that consistently stratify high- and low-risk subsets of AbP subjects with hazard ratios >6 (P < 0.01). The results suggest that these genes may be involved in T1D pathogenesis and potentially serve as excellent gene expression biomarkers to predict the risk of progression to clinical diabetes for AbP subjects.

PMID:
24595351
PMCID:
PMC4066338
DOI:
10.2337/db13-1716
[Indexed for MEDLINE]
Free PMC Article
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