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Background:The ADIPOQ gene encodes a fat-derived protein hormone with a preponderant role in the homeostasis of glucose and fatty acids. However, previous association studies between ADIPOQ genetic variants and metabolic disorders have shown controversial results. In this study, we evaluated the effect of the ADIPOQ-rs2241766 polymorphism on diverse biochemical parameters (i.e., insulin resistance, atherogenic index, overweight and obesity) in an adolescent population from Mexico. Methods: A cross-sectional study with convenience sampling was carried out in 356 adolescents from Northern Mexico. They were classified by sex and BMI-z score. The biochemical parameters were measured from blood samples using conventional methods. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: In low and normal weight groups, GG carriers had a significantly higher cholesterol level (P ≤ 0.05) than TG and TT carriers. However, there was no association between ADIPOQ-rs2241766 polymorphism and atherogenic index, overweight, or obesity. Conclusions: Our findings suggest that the cholesterol levels are under the influence of the ADIPOQ-rs2241766 polymorphism in Mexican adolescents and may explain how ADIPOQ variants increase the risk of developing metabolic disorders. Nevertheless, further studies are required to rule out the influence of other genetic and non-genetic factors.