BACKGROUND/OBJECTIVES: Adherence to treatment instructions is essential in managing chronic diseases related to obesity. One gene associated with adherence is the serotonin transporter (5-HTTLPR) gene, which has long (L) and short (S) alleles, resulting in LL, SL, and SS genotypes. Risk alleles for obesity include the R variant of the β3-adrenergic receptor () and the G variant of uncoupling protein 1 (). This study aimed to evaluate whether the S/L variant of , the R variant of , and the G variant of are associated with adherence to a weight loss program. To assess the factors influencing adherence, eating behavior was evaluated using the Eating Behavior Questionnaire (EBQ). METHODS: This study included 56 well-educated and middle-class women with a mean age of 57.3 ± 10 years and a mean BMI of 27.2 ± 5.6 kg/m. Long-read sequencing was used to analyze S/L mutations. Participants followed a six-month diet and exercise regimen for obesity management. Outcomes were assessed using clinical data and EBQ scores. Adherence was objectively measured by the reduction in body fat percentage. RESULTS: Participants were classified as SS (69.6%), SL (17.9%), or LL (12.5%). The R variant of was present in 34% of participants, with the G variant of in 75%. After the intervention, SS participants showed significantly greater reductions in weight and body fat percentage than LL participants ( < 0.05). Among EBQ items, significant improvements ( < 0.05) were observed in SS participants for eating as a diversion, feeling of fullness, bad eating habits, unsteady eating patterns, and total EBQ score. In SL participants, only bad eating habits improved, whereas no significant changes were observed in LL participants. Obesity risk alleles did not significantly affect clinical outcomes, though there may be small number bias. CONCLUSIONS: SS genotype participants demonstrated higher adherence to the weight loss program, leading to improved clinical outcomes and EBQ scores, independent of obesity risk genes.