Assessing the Role of <i>MC4R</i> Gene Variants and Dietary Habits in the Development of Obesity among Adolescents

Introduction: Obesity among adolescents is a growing public health concern, influenced by both genetic predispositions and modifiable lifestyle factors such as diet. Objective: To assess the association between MC4R gene variants and dietary habits in the development of obesity among adolescents in Pakistan. Hypothesis: This study hypothesizes that the C allele of MC4R rs17782313 and unhealthy dietary habits may interact to increase the risk of obesity among adolescents. Methodology: A descriptive cross-sectional study was conducted from November 2023 to October 2024 at Abdul Wali Khan University Mardan, including 260 adolescents aged 12–18 years. Convenience sampling was employed. Anthropometric data were collected, and body mass index (BMI) was calculated using WHO growth reference standards. Dietary patterns were assessed using a validated food frequency questionnaire (FFQ). The FFQ was pilot tested and adapted to the local population. Trained personnel collected anthropometric measurements using standardized protocols to minimize inter-observer variability. Saliva samples were genotyped for MC4R rs17782313 polymorphism using PCR-based methods at the Centre of Excellence in Molecular Biology, Lahore. Laboratory staff were blinded to participants’ obesity status. Genotyping call rates were 98.8%, and the genotype distribution was tested for Hardy-Weinberg equilibrium (p = 0.47). Statistical analysis was performed using SPSS version 26.0. Results: Of the 260 participants, 18.46% (n = 48) were obese and 21.54% (n = 56) were overweight. Genotypic distribution revealed 56.92% (n = 148) with TT, 30.00% (n = 78) with TC, and 13.08% (n = 34) with CC genotype. Obesity was present in 12.16% of TT, 25.64% of TC, and 29.41% of CC genotypes (p = 0.004). High fast food consumption (≥3 times/week) and daily intake of sugar-sweetened beverages were significantly associated with obesity (p < 0.01). Multivariate logistic regression adjusted for socioeconomic status, sleep duration, and screen time showed CC genotype (OR = 3.08), high fast food intake (OR = 2.97), and low physical activity (OR = 1.79) as independent predictors. The model fit was acceptable (Hosmer–Lemeshow p = 0.65; Nagelkerke R² = 0.38). Gene-diet interaction was tested using an interaction term in the logistic model. Conclusion: MC4R gene variants were associated with increased obesity prevalence in adolescents, especially in the presence of unhealthy dietary habits. Due to the cross-sectional nature of this study, causality cannot be inferred. Future prospective cohort studies are recommended to establish temporal relationships and validate these associations. These findings support the integration of genetic and lifestyle risk assessments for targeted obesity prevention strategies in youth.