title: 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.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors: Department of Nutrition, School of Public Health, University of Sao Paulo, Sao Paulo, Brazil.
authors: Maira L R
authors: ML
authors: Curti
authors: Marcelo M
authors: MM
authors: Rogero
authors: Valéria Troncoso
authors: VT
authors: Baltar
authors: Camila R
authors: CR
authors: Barros
authors: Antonela
authors: A
authors: Siqueira-Catania
authors: Sandra R G
authors: SR
authors: Ferreira
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000409:Alanine / Q000235:genetics; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D019943:Amino Acid Substitution / Q000235:genetics / Q000502:physiology; D016632:Apolipoprotein A-I / Q000235:genetics*; D001938:Brazil / Q000453:epidemiology; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008659:Metabolic Diseases / Q000453:epidemiology / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D011392:Proline / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D012307:Risk Factors; D040242:Risk Reduction Behavior; D055815:Young Adult
chemical_list: C505693:APOA1 protein, human; D016632:Apolipoprotein A-I; D047495:PPAR gamma; D011506:Proteins; D011392:Proline; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human; D000409:Alanine