Genetic background of type 1 diabetes mellitus: A review

Abstract

Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by the complete lack of insulin secretion due to the immune system’s destruction of insulin-producing pancreatic β-cells. Approximately 50% of the risk factors for T1DM are attributed to genetic susceptibility, with the remaining causes linked to epigenetic modifications and environmental factors. The major gene region involved in T1DM is the major histocompatibility (MHC) complex, which is the first region discovered, conferring 50% of the genetic risk, followed by the insulin (INS), cytotoxic T lymphocyte-associated protein (CTLA4), protein tyrosine phosphatase, non-receptor type 22 (PTPN22), interleukin 2 receptor alpha (IL2RA) and interferon-induced with helicase C domain (IFIH1) genes. The remaining genetic susceptibility has been uncovered through genome-wide association (GWA) studies, which have identified 120 single nucleotide polymorphisms (SNPs) associated with T1DM risk to date. Additionally, non-coding RNAs (ncRNAs) also play a role, affecting the expression of the genes involved in T1DM. Epigenetics bridges the gap between genetic predisposition and environmental factors, which act as a trigger for T1DM in susceptible individuals. In this paper, the major genes involved in the risk of T1DM are reviewed.