Association between single-nucleotide polymorphism in the islet amyloid polypeptide gene and beta-cell dysfunction in type 2 diabetes mellitus

Background and aim The rising worldwide incidence of type 2 diabetes mellitus (T2DM) highlights the importance of elucidating its genetic determinants, with particular focus on islet amyloid polypeptide (IAPP) and its impact on β-cell dysfunction. IAPP is co-released with insulin, aggregates into amyloid deposits in T2DM, potentially contributing to β-cell impairment. Genetic variations, such as single-nucleotide polymorphisms in the IAPP gene, may modulate this pathological process. We aimed to evaluate the relationship between the IAPP single-nucleotide polymorphisms rs77397980 and β-cell dysfunction in individuals with T2DM. Patients and methods This case–control study included 150 participants classified into three groups: normal glucose tolerance as a control group, impaired glucose tolerance, and diabetes based on oral glucose tolerance test results. Demographic, metabolic, and genetic data were collected, and rs77397980 was genotyped using real-time PCR. Statistical analysis assessed interactions between genotype and glucose levels on fasting glucose, insulin, and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Results The study showed no significant differences in genotype distribution (TT: 82%, TC: 18%) across groups ( P =0.6). While no significant interactions were found in normal glucose tolerance or impaired glucose tolerance groups, diabetic participants with higher glucose levels exhibited lower fasting insulin ( P =0.05) and HOMA-IR ( P =0.045) in TC carriers compared to TT homozygotes. Conclusion The IAPP rs77397980 TC genotype was associated with lower fasting insulin and HOMA-IR in diabetic individuals with severe hyperglycemia, suggesting a potential protective effect against insulin resistance under high glucose conditions.