Serotonin Transporter Gene Polymorphisms Predict Adherence to Weight Loss Programs Independently of Obesity-Related Genes

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 (β3AR) and the G variant of uncoupling protein 1 (UCP1). This study aimed to evaluate whether the S/L variant of 5-HTTLPR, the R variant of β3AR, and the G variant of UCP1 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: The study included 56 women with a mean age of 57.3±10 years and a mean BMI of 27.2±5.6 kg/m2. 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. Results: Participants were classified as SS (69.6%), SL (17.9%), or LL (12.5%). The R variant of β3AR was present in 34% of participants, with the G variant of UCP1 in 75%. After the intervention, SS participants showed significantly greater reductions in weight, body fat percentage, and waist circumference than LL participants (p < 0.05). Among EBQ items, significant improvements (p<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. 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.