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

Abstract

UNLABELLED:

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.

• Authors: Pablo Perez-Martinez, Javier Delgado-Lista, Antonio Garcia-Rios, Jolene Mc Monagle, Hanne L Gulseth, Jose M Ordovas, Danielle I Shaw, Brita Karlström, Beata Kiec-Wilk, Ellen E Blaak, Olfa Helal, Małgorzata Malczewska-Malec, Catherine Defoort, Ulf Risérus, Wim H M Saris, Julie A Lovegrove, Christian A Drevon, Helen M Roche, Jose Lopez-Miranda
• Journal: PloS one (PLoS One) Vol. 6 Issue 6 Pg. e20555 ( 2011) ISSN: 1932-6203 [Electronic] United States
• PMID: 21674002 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Blood Glucose
• Carrier Proteins
• Fatty Acids, Monounsaturated
• Fatty Acids, Omega-3
• Fatty Acids, Omega-6
• glucokinase regulatory protein
• C-Reactive Protein

Topics

• Adult
• Aged
• Blood Glucose (metabolism)
• C-Reactive Protein (metabolism)
• Carrier Proteins (genetics, metabolism)
• Fatty Acids, Monounsaturated (metabolism)
• Fatty Acids, Omega-3 (metabolism)
• Fatty Acids, Omega-6 (metabolism)
• Female
• Genetic Loci (genetics)
• Homeostasis (genetics)
• Humans
• Inflammation (complications, genetics, metabolism)
• Insulin Resistance (genetics)
• Male
• Metabolic Syndrome (complications, genetics, metabolism)
• Middle Aged
• Polymorphism, Genetic
• Protein Binding