FTO T/A and peroxisome proliferator-activated receptor-γ Pro12Ala polymorphisms but not ApoA1 -75 are associated with better response to lifestyle intervention in Brazilians at high cardiometabolic risk

摘要

Background: The role of obesity-related polymorphisms on weight loss and inflammatory responses to interventions is unclear. We investigated associations of certain polymorphisms with response to a lifestyle intervention. Methods: This 9-month intervention on diet and physical activity included 180 Brazilians at high cardiometabolic risk, genotyped for the fat mass and obesity-associated (FTO) T/A, peroxisome proliferator-activated receptor-γ (PPARγ) Pro12Ala, and ApoA1 -75G/A polymorphisms. Changes in metabolic and inflammatory variables were analyzed according to these polymorphisms. Results: The intervention resulted in lower energy intake and higher physical activity. Anthropometric measurements, 2-hr plasma glucose, insulin, high-density lipoprotein cholesterol (HDL-C), and apolipoprotein B (ApoB) improved significantly for the total sample, and these benefits were similar among genotypes. Only variant allele carriers of FTO T/A decreased fasting plasma glucose after intervention (99.9±1.3 to 95.6±1.4 mg/dL, P=0.021). Mean blood pressure reduced after intervention in variant allele carriers of the PPARγ Pro12Ala (109.4±2.1 to 101.3±2.1 mmHg, P<0.001). Improvement in lipid variables was not significant after adjustment for medication. Only the reference genotype of PPARγ Pro12Ala increased apolipoprotein A1 (ApoA1) after intervention (134.3±2.4 to 140.6±2.3 mg/dL, P<0.001). Only variant allele carriers of FTO reduced C-reactive protein (CRP) concentration (0.366±0.031 to 0.286±0.029 mg/dL, P=0.023). Conclusion: In Brazilian individuals, the FTO T/A polymorphism induces a favorable impact on inflammatory status and glucose metabolism. The reference genotype of PPARγ Pro12Ala seems to favor a better lipid profile, while the variant allele decreases blood pressure. Our data did not support benefits of the variant allele of ApoA1 -75G/A polymorphism. Further studies are needed to direct lifestyle intervention to subsets of individuals at cardiometabolic risk.