Dopaminergic system gene polymorphisms associated with severe obesity and related outcomes: A case-control study in...

Obesity has been increasing at an uncontrolled rate. Genetic variations have been shown to contribute to a higher risk of developing the condition, due to impaired satiety regulation, predisposition to addictive eating behaviors, or even specific personality traits. This study aimed to evaluate the influence of gene polymorphisms related to the dopaminergic system on developing severe obesity.

A sample of 332 individuals with severe obesity (cases, BMI≥35 kg/m²⁾ and 206 individuals with adequate weight (controls, 18.5 ≤BMI≤24.9 kg/m²⁾ was evaluated. Demographic, anthropometric, psychometric, biochemical, and hormonal aspects were collected. Genomic DNA was extracted and polymorphisms were amplified by PCR using Taqman® assays.

Our findings indicated an association between ANKK1 rs1800497 and susceptibility to severe obesity. The anthropometric parameters of weight and BMI were associated with ANKK1 rs1800497 and DRD2 rs1799732 variants, while COMT rs4680 was associated with BMI. The C-reactive protein was related to the DRD2 rs1799732 variant. DRD2 rs1076560 and ANKK1 rs1800497 were associated with an increased risk of developing depression. A distinct, pronounced association between genotypes and depression scores was also observed.

This study revealed that the ANKK1 rs1800497(AA) is a potential genetic risk marker associated with susceptibility to severe obesity and other parameters relevant to obesity and as with mental health. Furthermore, other evaluated polymorphisms also showed an association with characteristics related to obesity. Taken together, these findings support the hypothesis that dopaminergic genetic alterations are a potential contributor to the rise in obesity, related characteristics, and also impact the mental health of these individuals.