A Type 2 Diabetes-Associated Functional Regulatory Variant in a Pancreatic Islet Enhancer at the <i>ADCY5</i> Locus.

ABSTRACT: Molecular mechanisms remain unknown for most type 2 diabetes genome-wide association study identified loci. Variants associated with type 2 diabetes and fasting glucose levels reside in introns of ADCY5, a gene that encodes adenylate cyclase 5. Adenylate cyclase 5 catalyzes the production of cyclic AMP, which is a second messenger molecule involved in cell signaling and pancreatic β-cell insulin secretion. We demonstrated that type 2 diabetes risk alleles are associated with decreased ADCY5 expression in human islets and examined candidate variants for regulatory function. rs11708067 overlaps a predicted enhancer region in pancreatic islets. The type 2 diabetes risk rs11708067-A allele showed fewer H3K27ac ChIP-seq reads in human islets, lower transcriptional activity in repo

SUBMITTER: Roman TS 

PROVIDER: S-EPMC5860374 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature