Objective: To investigate the relationship between family history of type 2 diabetes (T2D) and insulin resistance. Bioinformatic approach was used to identify the risk pathways in subjects with a family history (FH) of T2D, and then functions of key driver genes were analyzed using gene expression profiles from Gene Expression Omnibus (GEO). Methods: Gene expression data set was retrieved using GSE 25462 at NCBI GEO. The data set contained 26 normoglycemic individuals with 1 or both parents having T2D (FH+) and 15 normoglycemic individuals with no one having diabetes in first-degree relatives(FH-). Insulin sensitivity was assessed by the Bergman minimal model from intravenous glucose tolerance test. Gene expression in quadriceps muscle biopsies was analyzed to identify the differentially expressed genes associated with insulin resistance. Gene set enrichment analysis and identification of risk pathways were used to explore the pathogenesis of T2D at molecular level. Results: Compared with FH- subjects, FH+ subjects were insulin resistant as demonstrated by a 41% reduction in insulin sensitivity(P<0.05). A total of 202 genes showed differential expression in our analysis. Five biological pathways of gene set enrichment in FH+ were identified, including hematopoiesis from multipotent stem cells, hematopoiesis from pluripotent stem cells, role of JAK1 and JAK3 in c-cytokine signaling, antiproliferative role of TOB in T cell signaling, and B cell development. Conclusions: Family history of T2D in normal subjects is associated with insulin resistance. Significantly enriched pathways identified by gene set enrichment analysis reveale that pathogenesis of T2D is associated with function of multipotent stem cells and immune status.
WANG Wei, WU Liping, ZHAO Yongju, CAO Jiumei
. Identification and function analysis of risk pathways in subjects with a family history of type 2 diabetes[J]. Journal of Diagnostics Concepts & Practice, 2016
, 15(05)
: 477
-481
.
DOI: 10.16150/j.1671-2870.2016.05.009
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