Genetic and Epigenetic Etiologies of Type 1 Diabetes Mellitus

Abstract

Numerous suspect genes associated with type 1 diabetes mellitus (T1DM) have been identified, suggesting a need to focus on the disease's causal genes and mechanisms. This necessitates an update to raise public awareness. This review articulates genes with mutations that predispose individuals to T1DM. We conducted a comprehensive search of academic databases, including Web of Science, Scopus, PubMed, and Google Scholar, for relevant materials. Available information indicates that at least 70 genes are suspected in the pathogenesis of T1DM. However, the most frequently implicated genes include human leukocyte antigen (HLA), insulin (INS), cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), and protein tyrosine phosphatase non-receptor type 22 (PTPN22). Mutations or variants in these genes may lead to insulin insufficiency and, consequently, T1DM by tricking immune cells, such as T-cells and B-cells, into attacking self-antigens and triggering the autoimmunity of beta cells. Furthermore, this pathophysiology can be mediated through aberrant epigenetic modifications, including DNA methylation, histone post-translational modifications, and noncoding RNAs, in the mentioned genes. Some of these pathophysiologies are gene-specific and may have an epigenetic origin that is reversible. In the event of an epigenetic origin, a treatment for T1DM that addresses the causal genes or reverses epigenetic changes and their mechanisms could yield improved outcomes. Medical professionals are encouraged to design therapeutic regimens that specifically target the mentioned genes and address the identified epigenetic alterations in individuals expressing such etiologies.