Bridging Genetics and Diagnosis in Type ۱ and Type ۲ Diabetes: The Role of Polymorphisms

Diabetes mellitus, encompassing type ۱ (T۱D) and type ۲ diabetes (T۲D), is a major global health burden with rapidly increasing prevalence. T۱D is characterized by autoimmune destruction of pancreatic β-cells, whereas T۲D primarily involves insulin resistance and β-cell dysfunction. Despite advances in clinical and molecular research, gaps remain in understanding the genetic architecture and gene–environment interactions driving disease onset and progression. This review summarizes current evidence on genetic polymorphisms associated with T۱D and T۲D, with a focus on their roles in disease susceptibility, complications, and potential therapeutic implications. In T۱D, variants in the HLA region, INS, and PTPN۲۲ have been strongly linked to autoimmunity and β-cell vulnerability. In T۲D, genes such as TCF۷L۲, KCNJ۱۱, SLC۳۰A۸, and EPO influence insulin secretion, glucose homeostasis, and risk modulation, with loss-of-function mutations in SLC۳۰A۸ showing protective effects. Emerging data highlight how genetic variants interact with zinc metabolism, inflammatory pathways, and environmental factors to shape disease heterogeneity. Additionally, polymorphisms in both T۱D- and T۲D-associated genes contribute to the risk of long-term complications, including nephropathy, retinopathy, and cardiovascular disease. By integrating evidence from genome-wide association studies, next-generation sequencing, and functional analyses, this review emphasizes the diagnostic and prognostic value of genetic markers. Understanding these genetic insights not only enhances risk prediction and early diagnosis but also supports the development of precision medicine approaches tailored to individual genetic backgrounds.

کلیدواژه ها:

Polymorphism ، Genetic ، Diabetes Mellitus ، Type ۱ ، Diabetes Mellitus ، Type ۲ ، Insulin-Secreting Cells ، Precision Medicine.