Genetic Variations in AMPK, FOXO3A, and POMC Increase the Risk of Extreme Obesity

Objective: Genetic variability significantly impacts metabolism, weight gain, and feeding behaviors, predisposing individuals to obesity. This study explored how variations in key genes related to obesity-FOXO3A (forkhead box O3), AMPK (protein kinase AMP-activated), and POMC (proopiomelanocortin)-are associated with extreme obesity (EOB). Methods: We conducted a case-control study with 251 EOB patients and 212 healthy controls with a body mass index (BMI) of less than 25 kg/m². We genotyped 10 single nucleotide variants (SNVs) using TaqMan-based assays. Results: Four SNVs-rs1536057 in FOXO3A, rs103685 in AMPK, rs934778, and rs6545975 in POMC-were associated with an increased risk of EOB. The strongest association was observed with rs934778 (POMC), which had a maximum odds ratio (OR) of 5.26 (95% CI: 2.86-9.09). While these genetic variations are closely linked to EOB, they do not affect serum glucose, triglycerides, HDL, LDL, BMI, or waist circumference. Conclusions: These findings indicate that factors beyond traditional metabolic pathways, potentially related to feeding behavior or hormonal regulation, may also link these genetic variations to obesity. Further research in a larger sample is essential to validate these findings and explore their potential to guide clinical interventions and public health strategies.