title: Fatty acids, IL6, and TNFalpha polymorphisms: an example of nutrigenetics in Crohn's disease.
abstract: OBJECTIVE
  The aim of this work was to study the interaction between genetic polymorphisms (single-nucleotide polymorphisms, SNPs) of pro- and anti-inflammatory cytokines and fat intake on the risk of developing Crohn's disease (CD) or modifying disease activity.
  
  
  METHODS
  Seven SNPs in interleukin 1 (IL1), tumor necrosis factor alpha (TNFalpha), lymphotoxin alpha (LTalpha), and IL6 genes were analyzed in 116 controls and 99 patients with CD. The type of fat intake was evaluated, and the interaction between SNPs and dietary fat in modulating disease activity was analyzed.
  
  
  RESULTS
  Individuals who were homozygous for the IL6-174G/C polymorphism had a six-fold higher risk for CD (odds ratio (OR)=6.1; 95% confidence interval (95% CI)=1.9-19.4), whereas the TT genotype on the TNFalpha-857C/T polymorphism was associated with more active disease (OR=10.4; 95% CI=1.1-94.1). A high intake of total, saturated, and monounsaturated fats, as well as a higher ratio of n-6/n-3 polyunsaturated fatty acid (PUFA), was associated with a more active phenotype (P<0.05). Furthermore, there was an interaction between dietary fat intake and SNPs, with a high intake of saturated and monounsaturated fats being associated with active disease, mainly in patients carrying the variant alleles of the 857 TNFalpha polymorphism (OR=6.0, 95% CI=1.4-26.2; OR=5.17; 95% CI=1.4-19.2, respectively) and the 174 IL6 polymorphism (OR=2.95; 95% CI=1.0-9.1; OR=3.21; 95% CI=1.0-10.4, respectively). Finally, low intake of n-3 PUFA and high n-6/n-3 PUFA ratio in patients with the TNFalpha 857 polymorphism were associated with higher disease activity (OR=3.6; 95% CI=1.0-13.0; OR=5.92; 95% CI=1.3-26.5, respectively).
  
  
  CONCLUSIONS
  These results show that different types of fat may interact with cytokine genotype, modulating disease activity.
authors: Department of Dietetics, Escola Superior de Tecnologia da Saúde de Lisboa, Unidade de Nutrição e Metabolismo do Instituto de Medicina Molecular da Universidade de Lisboa, 1990-096 Lisboa, Portugal. catarina.guerreiro@estesl.ipl.pt
authors: Catarina Sousa
authors: CS
authors: Guerreiro
authors: Paula
authors: P
authors: Ferreira
authors: Lourdes
authors: L
authors: Tavares
authors: Paula Moura
authors: PM
authors: Santos
authors: Manuela
authors: M
authors: Neves
authors: Miguel
authors: M
authors: Brito
authors: Marília
authors: M
authors: Cravo
mesh_terms: D000328:Adult; D003424:Crohn Disease / Q000209:etiology / Q000235:genetics*; D016207:Cytokines / Q000235:genetics; D004041:Dietary Fats / Q000494:pharmacology*; D005227:Fatty Acids / Q000494:pharmacology*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D054647:Nutrigenomics; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D016207:Cytokines; D004041:Dietary Fats; D005227:Fatty Acids; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha