Multiple genetic variants at the <i>SLC30A8</i> locus affect local super-enhancer activity and influence pancreatic β-cell survival and function.

ABSTRACT: Variants at the SLC30A8 locus are associated with type 2 diabetes (T2D) risk. The lead variant, rs13266634, encodes an amino acid change, Arg325Trp (R325W), at the C-terminus of the secretory granule-enriched zinc transporter, ZnT8. Although this protein-coding variant was previously thought to be the sole driver of T2D risk at this locus, recent studies have provided evidence for lowered expression of SLC30A8 mRNA in protective allele carriers. In the present study, combined allele-specific expression (cASE) analysis in human islets revealed multiple variants that influence SLC30A8 expression. Epigenomic mapping identified an islet-selective enhancer cluster at the SLC30A8 locus, hosting multiple T2D risk and cASE associations, which is spatially associated wit

SUBMITTER: Hu M 

PROVIDER: S-EPMC10369998 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature