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FTO RS17817449 VARIANT INCREASES THE RISK OF SEVERE OBESITY IN A BRAZILIAN COHORT: A CASE-CONTROL STUDY
Produção científica do Laboratório de Genética Humana.
Produção científica do Laboratório de Imunofarmacologia.
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Abstract
Purpose: Obesity is a complex disease caused by a combination of genetic, environmental, and epigenetic factors, and is associated with an increased risk of chronic diseases. The leptin-melanocortin pathway integrates peripheral signals about the body’s energy stores with a central neuronal circuit in the hypothalamus. This pathway has been extensively studied over the years, as genetic variations in genes related to it may play a crucial role in determining an individual’s susceptibility to obesity. Therefore, we analyzed the association between obesity and specific polymorphisms in leptin-melanocortin-related genes such as LEPR rs1137101, POMC rs1042571, LEP rs7799039, BDNF rs6265, FTO rs17817449, CART rs121909065, and NPY rs16147/rs5574. Patients and Methods: The study enrolled 501 participants from Rio de Janeiro, Brazil, with obesity class II or greater (BMI ≥ 35 kg/m2) and normal weight controls (18.5≤ BMI ≤ 24.9 kg/m2). We collected demographic, body composition, biochemical, and genotyping data by real-time PCR, and performed logistic and linear regression analyses to investigate the association of polymorphisms with severe obesity status and obesity-related quantitative parameters. Results: Individuals with severe obesity had significantly higher anthropometric measures, blood pressure, and biochemical levels. The FTO rs17817449 TT genotype was associated with a significantly higher risk of developing severe obesity, and distinct cytokine expression was observed across the FTO rs17817449 genotypes. The BDNF rs6265 dominant-model and NPY rs16147 CC genotypes were associated with triglyceride levels and childhood obesity, respectively. Finally, individuals with obesity were more likely to carry a greater number of risk alleles than those without obesity. Conclusion: Our study observed an important association between FTO rs17817449 polymorphism with obesity and obesity-related traits. Additionally, BDNF rs6265 dominant-model was associated with triglyceride serum levels, and NPY rs16147 may have a role in obesity onset.
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Taylor and Francis GroupDove Press
Citation
SALUM, Kaio Cezar Rodrigues et al. FTO rs17817449 variant increases the risk of severe obesity in a brazilian cohort: a case-control study. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, v. 18, p. 283-303, 31 Jan. 2025.DOI
10.2147/DMSO.S451401ISSN
1178-7007Notes
Produção científica do Laboratório de Epidemiologia de Malformações Congênitas.Produção científica do Laboratório de Genética Humana.
Produção científica do Laboratório de Imunofarmacologia.
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