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

Abstract

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.