title: PPARγ2 gene Pro12Ala and PPARα gene Leu162Val single nucleotide polymorphisms interact with dietary intake of fat in determination of plasma lipid concentrations.
abstract: OBJECTIVE
  The peroxisome proliferator-activated receptors (PPARs) are transcriptional regulators of lipid metabolism, activated by unsaturated fatty acids. We investigated independent and interactive effects of PPARγ2 gene PPARG Pro12Ala (rs1801282) andPPARαgene PPARA Leu162Val (rs1800206) genotypes with dietary intake of fatty acids on concentrations of plasma lipids in subjects of whom 47.5% had metabolic syndrome.
  
  
  METHODS
  The RISCK study is a parallel design, randomised controlled trial. Plasma lipids were quantified at baseline after a 4-week high saturated fatty acids diet and after three parallel 24-week interventions with reference (high saturated fatty acids), high monounsaturated fatty acids and low-fat diets. Single nucleotide polymorphisms were genotyped in 466 subjects.
  
  
  RESULTS
  At baseline, the PPARG Ala12allele was associated with increased plasma total cholesterol (n = 378; p = 0.04), LDL cholesterol (p = 0.05) and apoB (p =0.05) after adjustment for age, gender and ethnicity. At baseline, PPARA Leu162Val × PPARG Pro12Ala genotype interaction did not significantly influence plasma lipid concentrations. After dietary intervention, gene-gene interaction significantly influenced LDL cholesterol (p =0.0002) and small dense LDL as a proportion of LDL (p = 0.005) after adjustments.
  
  
  CONCLUSIONS
  Interaction between PPARG Pro12Ala and PPARA Leu162Val genotypes may influence plasma LDL cholesterol concentration and the proportion as small dense LDL after a high monounsaturated fatty acids diet.
authors.affiliation: Division of Diabetes and Nutritional Sciences, School of Medicine, King's College London, London, UK.
authors.forename: Aseel
authors.initials: A
authors.lastname: Alsaleh
authors.forename: Gary S
authors.initials: GS
authors.lastname: Frost
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Griffin
authors.forename: Julie A
authors.initials: JA
authors.lastname: Lovegrove
authors.forename: Susan A
authors.initials: SA
authors.lastname: Jebb
authors.forename: Thomas A B
authors.initials: TA
authors.lastname: Sanders
authors.forename: Sandra D
authors.initials: SD
authors.lastname: O'Dell
mesh_terms: D000328:Adult; D000368:Aged; D000409:Alanine / Q000235:genetics; D019943:Amino Acid Substitution / Q000235:genetics / Q000502:physiology; D004041:Dietary Fats / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D005260:Female; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D006801:Humans; D007930:Leucine / Q000235:genetics; D008055:Lipids / Q000032:analysis / Q000097:blood*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000502:physiology; D009994:Osmolar Concentration; D047493:PPAR alpha / Q000235:genetics*; D047495:PPAR gamma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D011392:Proline / Q000235:genetics; D014633:Valine / Q000235:genetics
chemical_list: D004041:Dietary Fats; D008055:Lipids; D047493:PPAR alpha; D047495:PPAR gamma; D011392:Proline; D007930:Leucine; D014633:Valine; D000409:Alanine