title: Genetic polymorphisms of tumor necrosis factor-alpha modify the association between dietary polyunsaturated fatty acids and fasting HDL-cholesterol and apo A-I concentrations.
abstract: BACKGROUND
  Heterogeneity in circulating lipid concentrations in response to dietary polyunsaturated fatty acids (PUFAs) may be due, in part, to genetic variations. Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that can induce hyperlipidemia and is known to be modulated by dietary PUFAs.
  
  
  OBJECTIVE
  The objective was to determine whether TNF-alpha genotypes modify the association between dietary PUFA intake and serum lipid concentrations.
  
  
  METHODS
  The study involved 53 men and 56 women aged 42-75 y with type 2 diabetes. Dietary intakes were assessed with the use of a 3-d food record, and blood samples were collected to determine fasting serum lipids. DNA was isolated from blood for genotyping by polymerase chain reaction-restriction fragment length polymorphism for the TNF-alpha -238G-->A and -308G-->A polymorphisms.
  
  
  RESULTS
  PUFA intake was positively associated with serum HDL cholesterol in carriers of the -238A allele (beta = 0.06 +/- 0.03 mmol/L per 1% of energy from PUFAs; P = 0.03), but negatively associated in those with the -238GG genotype (beta = -0.03 +/- 0.01, P = 0.03) (P = 0.004 for interaction). PUFA intake was inversely associated with HDL cholesterol in carriers of the -308A allele (beta = -0.07 +/- 0.02, P = 0.002), but not in those with the -308GG genotype (beta = 0.02 +/- 0.02, P = 0.13) (P = 0.001 for interaction). A stronger gene x diet interaction was observed when the polymorphisms at the 2 positions (-238/-308) were combined (P = 0.0003). Similar effects were observed for apolipoprotein A-I, but not with other dietary fatty acids and serum lipids.
  
  
  CONCLUSIONS
  TNF-alpha genotypes modify the relation between dietary PUFA intake and HDL-cholesterol concentrations. These findings suggest that genetic variations affecting inflammation may explain some of the inconsistencies between previous studies relating PUFA intake and circulating HDL.
authors.affiliation: Department of Nutritional Sciences and Nutrition, University of Toronto, Toronto, Canada.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Fontaine-Bisson
authors.forename: Thomas M S
authors.initials: TM
authors.lastname: Wolever
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Chiasson
authors.forename: Rémi
authors.initials: R
authors.lastname: Rabasa-Lhoret
authors.forename: Pierre
authors.initials: P
authors.lastname: Maheux
authors.forename: Robert G
authors.initials: RG
authors.lastname: Josse
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Leiter
authors.forename: N Wilson
authors.initials: NW
authors.lastname: Rodger
authors.forename: Edmond A
authors.initials: EA
authors.lastname: Ryan
authors.forename: Philip W
authors.initials: PW
authors.lastname: Connelly
authors.forename: Paul N
authors.initials: PN
authors.lastname: Corey
authors.forename: Ahmed
authors.initials: A
authors.lastname: El-Sohemy
mesh_terms: D000368:Aged; D016632:Apolipoprotein A-I / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D015930:Diet Records; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage*; D005215:Fasting / Q000097:blood; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D054647:Nutrigenomics; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*