title: Additive effect of polymorphisms in the IL-6, LTA, and TNF-{alpha} genes and plasma fatty acid level modulate risk for the metabolic syndrome and its components.
abstract: BACKGROUND
  Cytokine polymorphisms and dietary fat composition may influence the risk of the metabolic syndrome (MetS).
  
  
  OBJECTIVE
  The objective of the study was to determine the relationship between lymphotoxin-alpha (LTA), TNF-alpha, and IL-6 gene polymorphisms with MetS risk and investigate whether plasma fatty acid composition, a biomarker of dietary fat intake, modulated these associations.
  
  
  METHODS
  Polymorphisms (LTA rs915654, TNF-alpha rs1800629, IL-6 rs1800797), biochemical measurements, and plasma fatty acids were determined in the LIPGENE-SU.VI.MAX study of MetS cases and matched controls (n = 1754).
  
  
  RESULTS
  LTA rs915654 minor A allele carriers and TNF-alpha rs1800629 major G allele homozygotes had increased MetS risk [odds ratio (OR) 1.37 (confidence interval [CI] 1.12-1.66), P = 0.002 and OR 1.35 (CI 1.08-1.70), P = 0.009] compared with their TT homozygotes and A allele carriers. Possession of the IL-6 rs1800797 GG genotype by the LTA and TNF-alpha risk genotype carriers further increased risk of the MetS [OR 2.10 (CI 1.19-3.71) P = 0.009], fasting hyperglycemia [OR 2.65 (CI 1.12-6.28), P = 0.027], high systolic blood pressure [OR 1.99 (CI 1.07-3.72), P = 0.03], and abdominal obesity [OR 1.52 (CI 1.01-2.28), P = 0.04]. Plasma polyunsaturated to saturated fat ratio exacerbated these effects; subjects in the lowest 50th percentile had even greater risk of the MetS [OR 4.40 (CI 1.55-12.45), P = 0.005], fasting hyperglycemia, high systolic blood pressure, and abdominal obesity (P < 0.05).
  
  
  CONCLUSIONS
  LTA, TNF-alpha, and IL-6 genotype interactions increased MetS risk, which was further exacerbated by a low plasma polyunsaturated to saturated fat exposure, indicating important modulation of genetic risk by dietary fat exposure.
authors.affiliation: Nutrigenomics Research Group, University College Dublin School of Public Health and Population Science, University College Dublin Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Phillips
authors.forename: Louisa
authors.initials: L
authors.lastname: Goumidi
authors.forename: Sandrine
authors.initials: S
authors.lastname: Bertrais
authors.forename: Jane F
authors.initials: JF
authors.lastname: Ferguson
authors.forename: Martyn R
authors.initials: MR
authors.lastname: Field
authors.forename: Enda D
authors.initials: ED
authors.lastname: Kelly
authors.forename: John
authors.initials: J
authors.lastname: Mehegan
authors.forename: Gina M
authors.initials: GM
authors.lastname: Peloso
authors.forename: L Adrienne
authors.initials: LA
authors.lastname: Cupples
authors.forename: Jian
authors.initials: J
authors.lastname: Shen
authors.forename: Jose M
authors.initials: JM
authors.lastname: Ordovas
authors.forename: Ross
authors.initials: R
authors.lastname: McManus
authors.forename: Serge
authors.initials: S
authors.lastname: Hercberg
authors.forename: Henri
authors.initials: H
authors.lastname: Portugal
authors.forename: Denis
authors.initials: D
authors.lastname: Lairon
authors.forename: Richard
authors.initials: R
authors.lastname: Planells
authors.forename: Helen M
authors.initials: HM
authors.lastname: Roche
mesh_terms: D000483:Alleles; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D004041:Dietary Fats; D005227:Fatty Acids / Q000097:blood*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000097:blood; D015850:Interleukin-6 / Q000235:genetics*; D008233:Lymphotoxin-alpha / Q000235:genetics*; D024821:Metabolic Syndrome / Q000097:blood* / Q000235:genetics*; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012044:Regression Analysis; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D055105:Waist Circumference
chemical_list: D004041:Dietary Fats; D005227:Fatty Acids; D007328:Insulin; D015850:Interleukin-6; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein