TY - JOUR
T1 - Glucokinase regulatory protein genetic variant interacts with Omega-3 PUFA to influence insulin resistance and inflammation in metabolic syndrome
AU - Perez - Martinez, P.
AU - Delgado - Lista, J.
AU - Garcia - Rios, A.
AU - Mc Monagle, J.
AU - Gulseth, H.L.
AU - Ordovas, J.M.
AU - Shaw, D.I.
AU - Karlstrom, B.
AU - Kiec - Wilk, B.
AU - Blaak, E.E.
AU - Helal, O.
AU - Malszewska - Malec, M.
AU - Defoort, C.
AU - Riserus, U.
AU - Saris, W.H.
AU - Lovegrove, J.A.
AU - Drevon, C.A.
AU - Roche, H.M.
AU - Lopez - Miranda, J.
PY - 2011/6/6
Y1 - 2011/6/6
N2 - 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.
AB - 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.
KW - C-REACTIVE PROTEIN
KW - POLYUNSATURATED FATTY-ACIDS
KW - FASTING PLASMA-GLUCOSE
KW - TYPE-2 DIABETES RISK
KW - CARDIOVASCULAR-DISEASE
KW - TRIGLYCERIDE LEVELS
KW - LOCI
KW - OMEGA-3-FATTY-ACIDS
KW - ADULTS
KW - POLYMORPHISMS
U2 - 10.1371/journal.pone.0020555
DO - 10.1371/journal.pone.0020555
M3 - Article
SN - 1932-6203
VL - 6
JO - PLOS ONE
JF - PLOS ONE
IS - 6
M1 - 20555
ER -