Single nucleotide polymorphisms associated with susceptibility to developing type 2 diabetes mellitus

Abstract

Introduction. Type 2 diabetes mellitus (T2DM) is a chronic and multifactorial metabolic disease characterized by sustained hyperglycemia, insulin resistance, and progressive β-cell dysfunction. In Latin America and particularly in Ecuador T2DM represents a growing public health concern. Among genetic determinants, single nucleotide polymorphisms (SNPs) have emerged as key markers influencing insulin secretion, lipid metabolism, and insulin sensitivity. Objective. To analyze the main SNPs associated with genetic susceptibility to developing T2DM, considering both risk and protective variants reported between 2019 and 2024. Methodology. A systematic bibliographic review was conducted following PRISMA guidelines. Searching was performed in PubMed, Scielo, Web of Science and the Virtual Health Library (VHL), using MeSH/DeCS terms combined with Boolean operators. Included studies were quantitative originals and meta-analyses published between 2019 and 2024 that evaluated associations between SNPs and T2DM and reported statistical measures (OR, CI, p-value). Narrative reviews without primary data, studies in animals, duplicates, and articles outside the time frame were excluded. A total of 17 studies met the inclusion criteria. Results. SNPs associated with impaired insulin secretion included KCNJ11 rs5210, CYP2D6 rs1065852, ABCC8 rs1799854, and TCF7L2 rs7903146, all reporting significant associations (OR 1.34–2.07), consistent with alterations in K-ATP channel function or incretin-mediated pathways. Variants linked to insulin resistance included ADIPOQ rs17846866/rs1501299, FTO rs9939609/rs17817449, IGF2BP2 rs6769511, and HHEX rs1111875, associated with adipogenesis, metabolic inflammation, and hepatic regulation (OR 1.37–3.02). Conversely, PPARG rs3856806 demonstrated a protective effect (OR=0.82), suggesting beneficial modulation of insulin sensitivity and lipid metabolism. Conclusion. The analyzed SNPs are relevant biomarkers for understanding genetic susceptibility to T2DM; however, their clinical applicability remains limited due to complex gene–environment interactions. Strengthening longitudinal research in Latin American populations is recommended to develop population-specific polygenic risk models and advance precision medicine approaches. General Area of Study: Clinical Laboratory. Specific area of study: Molecular biology. Type of study: Systematic bibliographic review.