title: Dietary fat intake and polymorphisms at the PPARG locus modulate BMI and type 2 diabetes risk in the D.E.S.I.R. prospective study.
abstract: BACKGROUND
  Fat-rich diets are involved in many disorders such as obesity and type 2 diabetes (T2D). The Pro12Ala variant of peroxisome proliferator-activated receptor-γ (PPARγ) is known to modulate body mass index (BMI) and T2D risk.
  
  
  OBJECTIVE
  Our aim was to study the interaction effect between PPARγ gene (PPARG) polymorphisms Pro12Ala and 1431C>T and fat intake on incident T2D and BMI in a 9-year prospective cohort drawn from the French general population, the D.E.S.I.R. (Data from an Epidemiological Study on the Insulin Resistance Syndrome) study (n=4676).
  
  
  METHODS
  Nutritional intake was assessed by a food frequency self-questionnaire completed by each participant. Statistical analyses included logistic regression, analysis of covariance and haplotype analysis, with adjustment for confounding variables.
  
  
  RESULTS
  A high fat consumption (the third sex-specific tertile of fat intake, as a percentage of energy intake) was associated with an increased T2D risk among ProPro and CC homozygotes (P(interaction)=0.05, odds ratio (OR) (95% confidence interval (95% CI))=1.73 (1.19-2.52) P=0.004 and OR=1.85 (1.27-2.71) P=0.001, respectively) but not in Ala and T carriers. There was a significant interaction effect between Pro12Ala and 1431C>T on BMI (P(interaction)=0.004); Ala was associated with lower BMI in CC homozygotes and with higher BMI in T carriers while the opposite was found for ProPro. There was also an interaction effect between Pro12Ala and dietary fat intake on BMI (P(interaction)=0.02); AlaAla individuals had a higher BMI than Pro carriers among high fat consumers (27.1 ± 1.0 versus 24.9 ± 0.1 for AlaAla and Pro+, respectively). There was no interaction effect between the 1431C>T single-nucleotide polymorphism and fat intake on BMI.
  
  
  CONCLUSIONS
  Our results indicate strong genetic and nutritional interaction effects on BMI and T2D risk at the PPARG locus in a general population.
authors.affiliation: INSERM, U695 (Genetic determinants of type 2 diabetes and its vascular complications), Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Lamri
authors.forename: C
authors.initials: C
authors.lastname: Abi Khalil
authors.forename: R
authors.initials: R
authors.lastname: Jaziri
authors.forename: G
authors.initials: G
authors.lastname: Velho
authors.forename: O
authors.initials: O
authors.lastname: Lantieri
authors.forename: S
authors.initials: S
authors.lastname: Vol
authors.forename: P
authors.initials: P
authors.lastname: Froguel
authors.forename: B
authors.initials: B
authors.lastname: Balkau
authors.forename: M
authors.initials: M
authors.lastname: Marre
authors.forename: F
authors.initials: F
authors.lastname: Fumeron
mesh_terms: D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D004041:Dietary Fats / Q000494:pharmacology; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology / Q000235:genetics*; D047495:PPAR gamma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011795:Surveys and Questionnaires
chemical_list: D004041:Dietary Fats; D047495:PPAR gamma