title: Gene-nutrient interactions in the metabolic syndrome: single nucleotide polymorphisms in ADIPOQ and ADIPOR1 interact with plasma saturated fatty acids to modulate insulin resistance.
abstract: BACKGROUND
  Progression of the metabolic syndrome (MetS) is determined by genetic and environmental factors. Gene-environment interactions may be important in modulating the susceptibility to the development of MetS traits.
  
  
  OBJECTIVE
  Gene-nutrient interactions were examined in MetS subjects to determine interactions between single nucleotide polymorphisms (SNPs) in the adiponectin gene (ADIPOQ) and its receptors (ADIPOR1 and ADIPOR2) and plasma fatty acid composition and their effects on MetS characteristics.
  
  
  METHODS
  Plasma fatty acid composition, insulin sensitivity, plasma adiponectin and lipid concentrations, and ADIPOQ, ADIPOR1, and ADIPOR2 SNP genotypes were determined in a cross-sectional analysis of 451 subjects with the MetS who participated in the LIPGENE (Diet, Genomics, and the Metabolic Syndrome: an Integrated Nutrition, Agro-food, Social, and Economic Analysis) dietary intervention study and were repeated in 1754 subjects from the LIPGENE-SU.VI.MAX (SUpplementation en VItamines et Minéraux AntioXydants) case-control study (http://www.ucd.ie/lipgene).
  
  
  RESULTS
  Single SNP effects were detected in the cohort. Triacylglycerols, nonesterified fatty acids, and waist circumference were significantly different between genotypes for 2 SNPs (rs266729 in ADIPOQ and rs10920533 in ADIPOR1). Minor allele homozygotes for both of these SNPs were identified as having degrees of insulin resistance, as measured by the homeostasis model assessment of insulin resistance, that were highly responsive to differences in plasma saturated fatty acids (SFAs). The SFA-dependent association between ADIPOR1 rs10920533 and insulin resistance was replicated in cases with MetS from a separate independent study, which was an association not present in controls.
  
  
  CONCLUSIONS
  A reduction in plasma SFAs could be expected to lower insulin resistance in MetS subjects who are minor allele carriers of rs266729 in ADIPOQ and rs10920533 in ADIPOR1. Personalized dietary advice to decrease SFA consumption in these individuals may be recommended as a possible therapeutic measure to improve insulin sensitivity. This trial was registered at clinicaltrials.gov as NCT00429195.
authors.affiliation: University College Dublin, Dublin, Ireland.
authors.forename: Jane F
authors.initials: JF
authors.lastname: Ferguson
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Phillips
authors.forename: Audrey C
authors.initials: AC
authors.lastname: Tierney
authors.forename: Pablo
authors.initials: P
authors.lastname: Pérez-Martínez
authors.forename: Catherine
authors.initials: C
authors.lastname: Defoort
authors.forename: Olfa
authors.initials: O
authors.lastname: Helal
authors.forename: Denis
authors.initials: D
authors.lastname: Lairon
authors.forename: Richard
authors.initials: R
authors.lastname: Planells
authors.forename: Danielle I
authors.initials: DI
authors.lastname: Shaw
authors.forename: Julie A
authors.initials: JA
authors.lastname: Lovegrove
authors.forename: Ingrid Mf
authors.initials: IM
authors.lastname: Gjelstad
authors.forename: Christian A
authors.initials: CA
authors.lastname: Drevon
authors.forename: Ellen E
authors.initials: EE
authors.lastname: Blaak
authors.forename: Wim Hm
authors.initials: WH
authors.lastname: Saris
authors.forename: Iwona
authors.initials: I
authors.lastname: Leszczynska-Golabek
authors.forename: Beata
authors.initials: B
authors.lastname: Kiec-Wilk
authors.forename: Ulf
authors.initials: U
authors.lastname: Risérus
authors.forename: Brita
authors.initials: B
authors.lastname: Karlström
authors.forename: José Lopez-
authors.initials: JL
authors.lastname: Miranda
authors.forename: Helen M
authors.initials: HM
authors.lastname: Roche
mesh_terms: D052242:Adiponectin / Q000235:genetics*; D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D004041:Dietary Fats / Q000097:blood*; D018450:Disease Progression; D005227:Fatty Acids / Q000097:blood*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006720:Homozygote; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D054419:Receptors, Adiponectin / Q000235:genetics*; D014280:Triglycerides / Q000097:blood; D055105:Waist Circumference / Q000235:genetics
chemical_list: D052242:Adiponectin; D004041:Dietary Fats; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D054419:Receptors, Adiponectin; D014280:Triglycerides