Glucokinase regulatory protein genetic variant interacts with Omega-3 PUFA to influence insulin resistance and inflammation in metabolic syndrome

P. Perez - Martinez, J. Delgado - Lista, A. Garcia - Rios, J. Mc Monagle, H.L. Gulseth, J.M. Ordovas, D.I. Shaw, B. Karlstrom, B. Kiec - Wilk, E.E. Blaak, O. Helal, M. Malszewska - Malec, C. Defoort, U. Riserus, W.H. Saris, J.A. Lovegrove, C.A. Drevon, H.M. Roche, J. Lopez - Miranda

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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. DESIGN: 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT00429195.
Original languageEnglish
Article number20555
Number of pages7
JournalPLOS ONE
Volume6
Issue number6
DOIs
Publication statusPublished - 6 Jun 2011

Keywords

  • C-REACTIVE PROTEIN
  • POLYUNSATURATED FATTY-ACIDS
  • FASTING PLASMA-GLUCOSE
  • TYPE-2 DIABETES RISK
  • CARDIOVASCULAR-DISEASE
  • TRIGLYCERIDE LEVELS
  • LOCI
  • OMEGA-3-FATTY-ACIDS
  • ADULTS
  • POLYMORPHISMS

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