Genes affecting β-cell function in type 1 diabetes

Curr Diab Rep. 2015 Nov;15(11):97. doi: 10.1007/s11892-015-0655-9.

Abstract

Type 1 diabetes (T1D) is a multifactorial disease resulting from an immune-mediated destruction of the insulin-producing pancreatic β cells. Several environmental and genetic risk factors predispose to the disease. Genome-wide association studies (GWAS) have identified around 50 genetic regions that affect the risk of developing T1D, but the disease-causing variants and genes are still largely unknown. In this review, we discuss the current status of T1D susceptibility loci and candidate genes with focus on the β cell. At least 40 % of the genes in the T1D susceptibility loci are expressed in human islets and β cells, where they according to recent studies modulate the β-cell response to the immune system. As most of the risk variants map to noncoding regions of the genome, i.e., promoters, enhancers, intergenic regions, and noncoding genes, their possible involvement in T1D pathogenesis as gene regulators will also be addressed.

Keywords: CTSH; Candidate genes; GWAS; Noncoding RNA; Pancreatic islets; T1D.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 1 / genetics*
  • Gene Expression Regulation*
  • Genome-Wide Association Study
  • Humans
  • Insulin / genetics
  • Insulin-Secreting Cells / metabolism*
  • Insulin-Secreting Cells / pathology
  • RNA, Untranslated / genetics

Substances

  • Insulin
  • RNA, Untranslated