title: Fat intake interacts with polymorphisms of Caspase9, FasLigand and PPARgamma apoptotic genes in modulating Crohn's disease activity.
abstract: OBJECTIVE
  Crohn's disease (CD) is a multifactorial disease where resistance to apoptosis is one major defect. Also, dietary fat intake has been shown to modulate disease activity. We aimed to explore the interaction between four single nucleotide polymorphisms (SNPs) in apoptotic genes and dietary fat intake in modulating disease activity in CD patients.
  
  
  METHODS
  Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) techniques were used to analyze Caspase9+93C/T, FasLigand-843C/T, Peroxisome Proliferator-Activated Receptor gamma+161C/T and Peroxisome Proliferator-Activated Receptor gamma Pro12Ala SNPs in 99 patients with CD and 116 healthy controls. Interactions between SNPs and fat intake in modulating disease activity were analyzed using regression analysis.
  
  
  RESULTS
  None of the polymorphisms analyzed influenced disease susceptibility and/or activity, but a high intake of total, saturated and monounsaturated fats and a higher ratio of n-6/n-3 polyunsaturated fatty acids(PUFA), was associated with a more active phenotype (p < 0.05). We observed that the detrimental effect of a high intake of total and trans fat was more marked in wild type carriers of the Caspase9+93C/T polymorphism [O.R(95%CI) 4.64(1.27-16.89) and O.R(95%CI) 4.84(1.34-17.50)]. In the Peroxisome Proliferator-Activated Receptor gamma Pro12Ala SNP, we also observed that a high intake of saturated and monounsaturated fat was associated to a more active disease in wild type carriers [OR(95%CI) 4.21(1.33-13.26) and 4.37(1.52-12.51)]. Finally, a high intake of n-6 PUFA was associated with a more active disease in wild type carriers for the FasLigand-843C/T polymorphism [O.R(95%CI) 5.15(1.07-24.74)].
  
  
  CONCLUSIONS
  To our knowledge, this is the first study to disclose a synergism between fat intake and SNPs in apoptotic genes in modulating disease activity in CD patients.
authors.affiliation: Escola Superior de Tecnologia da Saúde de Lisboa, Lisboa, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Ferreira
authors.forename: Marília
authors.initials: M
authors.lastname: Cravo
authors.forename: Catarina Sousa
authors.initials: CS
authors.lastname: Guerreiro
authors.forename: Lourdes
authors.initials: L
authors.lastname: Tavares
authors.forename: Paula Moura
authors.initials: PM
authors.lastname: Santos
authors.forename: Miguel
authors.initials: M
authors.lastname: Brito
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D053453:Caspase 9 / Q000235:genetics*; D003424:Crohn Disease / Q000235:genetics* / Q000378:metabolism*; D004032:Diet; D004041:Dietary Fats / Q000378:metabolism*; D053222:Fas Ligand Protein / Q000235:genetics*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis
chemical_list: D004041:Dietary Fats; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D005231:Fatty Acids, Unsaturated; D047495:PPAR gamma; C506433:CASP9 protein, human; D053453:Caspase 9