TITLE:
Expression profiling of putative type 2 diabetes susceptibility genes in human islets and in rat beta cell lines
AUTHORS:
Faer Morrison, Jonathan Locke, Anna Murray, Lorna W. Harries
KEYWORDS:
Human; Type 2 Diabetes; Islet; GWAS; Gene Expression
JOURNAL NAME:
Journal of Diabetes Mellitus,
Vol.3 No.1,
February
26,
2013
ABSTRACT: Over 50
single nucleotide polymorphisms (SNPs) have been identified by genome wide association studies (GWAS) to be
associated with susceptibility to type 2 diabetes (T2D); however the causal
gene in most cases is not known. In this study we sought to identify which may
be the most likely causal genes at five T2D GWAS loci by measuring their
expression in control and T2D islets, as well as observing their regulation by
glucose. We measured the expression of ten genes at five loci (CDKN2A/2B, CDC123/CAMK-1D, HHEX/IDE, TSPAN8/LGR5, and DGKB/TMEM 195), in control and human
pancreatic islets by real-time PCR. We then measured the expression of these
genes in the rodent pancreatic beta cell line INS-1 exposed to 5.6 mmol/l, 11 mmol/l
and 28 mmol/l glucose for 48 hours. We found differential expression of the
longest isoform of CDKN2B specifically between control and T2D
human islets, whereas the shortest isoform of this gene had no expression in
islets. Tmem195 was the only gene to
show differential expression in response to increasing glycemia in INS-1 cells
under the conditions described. Our study is an example of how the differential
expression of genes in loci spanning more than one gene can aid identification
of the more likely causal gene.