title: Glucokinase regulatory protein genetic variant interacts with omega-3 PUFA to influence insulin resistance and inflammation in metabolic syndrome.
abstract: Glucokinase Regulatory Protein (GCKR) plays a central role regulating both hepatic triglyceride and glucose metabolism. Fatty acids are key metabolic regulators, which interact with genetic factors and influence glucose metabolism and other metabolic traits. Omega-3 polyunsaturated fatty acids (n-3 PUFA) have been of considerable interest, due to their potential to reduce metabolic syndrome (MetS) risk.
  
  
  OBJECTIVE
  To examine whether genetic variability at the GCKR gene locus was associated with the degree of insulin resistance, plasma concentrations of C-reactive protein (CRP) and n-3 PUFA in MetS subjects.
  
  
  METHODS
  Homeostasis model assessment of insulin resistance (HOMA-IR), HOMA-B, plasma concentrations of C-peptide, CRP, fatty acid composition and the GCKR rs1260326-P446L polymorphism, were determined in a cross-sectional analysis of 379 subjects with MetS participating in the LIPGENE dietary cohort.
  
  
  RESULTS
  Among subjects with n-3 PUFA levels below the population median, carriers of the common C/C genotype had higher plasma concentrations of fasting insulin (P = 0.019), C-peptide (P = 0.004), HOMA-IR (P = 0.008) and CRP (P = 0.032) as compared with subjects carrying the minor T-allele (Leu446). In contrast, homozygous C/C carriers with n-3 PUFA levels above the median showed lower plasma concentrations of fasting insulin, peptide C, HOMA-IR and CRP, as compared with individuals with the T-allele.
  
  
  CONCLUSIONS
  We have demonstrated a significant interaction between the GCKR rs1260326-P446L polymorphism and plasma n-3 PUFA levels modulating insulin resistance and inflammatory markers in MetS subjects. Further studies are needed to confirm this gene-diet interaction in the general population and whether targeted dietary recommendations can prevent MetS in genetically susceptible individuals.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00429195.
authors.affiliation: Lipid and Atherosclerosis Unit, IMIBIC/Reina Sofia University Hospital/University of Cordoba, and CIBER Fisiopatologia Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Cordoba, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Perez-Martinez
authors.forename: Javier
authors.initials: J
authors.lastname: Delgado-Lista
authors.forename: Antonio
authors.initials: A
authors.lastname: Garcia-Rios
authors.forename: Jolene
authors.initials: J
authors.lastname: Mc Monagle
authors.forename: Hanne L
authors.initials: HL
authors.lastname: Gulseth
authors.forename: Jose M
authors.initials: JM
authors.lastname: Ordovas
authors.forename: Danielle I
authors.initials: DI
authors.lastname: Shaw
authors.forename: Brita
authors.initials: B
authors.lastname: Karlström
authors.forename: Beata
authors.initials: B
authors.lastname: Kiec-Wilk
authors.forename: Ellen E
authors.initials: EE
authors.lastname: Blaak
authors.forename: Olfa
authors.initials: O
authors.lastname: Helal
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Malczewska-Malec
authors.forename: Catherine
authors.initials: C
authors.lastname: Defoort
authors.forename: Ulf
authors.initials: U
authors.lastname: Risérus
authors.forename: Wim H M
authors.initials: WH
authors.lastname: Saris
authors.forename: Julie A
authors.initials: JA
authors.lastname: Lovegrove
authors.forename: Christian A
authors.initials: CA
authors.lastname: Drevon
authors.forename: Helen M
authors.initials: HM
authors.lastname: Roche
authors.forename: Jose
authors.initials: J
authors.lastname: Lopez-Miranda
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D043371:Fatty Acids, Omega-6 / Q000378:metabolism; D005260:Female; D056426:Genetic Loci / Q000235:genetics; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011485:Protein Binding
chemical_list: D001786:Blood Glucose; D002352:Carrier Proteins; D005229:Fatty Acids, Monounsaturated; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; C080906:glucokinase regulatory protein; D002097:C-Reactive Protein