The n-3 long-chain PUFAs modulate the impact of the GCKR Pro446Leu polymorphism on triglycerides in adolescents

Abstract

Dietary n-3 long-chain PUFAs (LC-PUFAs) are associated with improvement in the parameters of the metabolic syndrome (MetS). Glucokinase regulatory protein (GCKR) is a key protein regulating intracellular glucose disposal. Our aim was to investigate: i ) the relationship between the GCKR rs1260326 (Pro446Leu) polymorphism and parameters of the MetS; and ii ) a potential infl uence of n-3 and n-6 LC-PUFA levels on this relationship in the HELENA study (1,155 European adolescents). Linear regression analyses were performed to study the association between rs1260326 and the outcomes of interest. Interactions between rs1260326 and LC-PUFA levels on outcomes were explored. The T allele of rs1260326 was associated with higher serum TG concentrations compared with the C allele. In contrast to n-6 LC-PUFA levels, a signifi cant interaction ( P = 0.01) between rs1260326 and total n-3 LC-PUFA levels on serum TG concentrations was observed. After stratifi cation on the n-3 LC-PUFA median values, the association between rs1260326 and TG concentration was signifi cant only in the group with high n-3 LC-PUFA levels. In conclusion, this is the fi rst evidence that n-3 LC-PUFAs may modulate the impact of the GCKR The HELENA study has taken place with the Financial support of the European Community Sixth RTD Framework Programme (Contract FOOD-CT-2005-007034

Association of common gene variants in glucokinase regulatory protein with cardiorenal disease: A systematic review and meta-analysis

“…Although ancestry did not account for the moderate-to-high heterogeneity, the number of studies was too small to make strong inferences. Furthermore, differences in diet could contribute to the observed heterogeneity given the previously reported GCKR -diet interaction on plasma triglycerides levels [ 55 , 56 ]. It is, however, unlikely that these factors truly account for the opposing effect sizes that were present in the individual studies, e.g.…”

Asymptomatic Carotid Atherosclerosis Cardiovascular Risk Factors and Common Hypertriglyceridemia Genetic Variants in Patients with Systemic Erythematosus Lupus

“…The homozygous TT allele of the GCKR rs1260326 led to a destabilization of the glucokinase binding interface. Increased hepatic glucokinase activity results in higher fasting serum TG concentration and lower glucose concentration (38,39). In a meta-analysis of 46 genome-wide association studies a signi cant association between the homozygous TT allele of GCKR rs1260326 and higher circulating TG levels was observed (40) although the atherogenic effect of this variant is controversial (41)(42)(43).…”

A Genetic Score of Predisposition to Low-Grade Inflammation Associated with Obesity May Contribute to Discern Population at Risk for Metabolic Syndrome

“…First, rs1260326 located in glucokinase regulator (GCKR) gene involves the change of the amino acid Proline at position 466 for Leucine and has been strongly associated with the risk of elevated CRP [ 49 ], dyslipidemia [ 49 , 50 , 51 , 52 ] and type 2 diabetes [ 53 ] in different GWAs. Nevertheless, two additional studies pointed out a potential modulation of omega 3 PUFAs on lipid profile and inflammatory plasma biomarkers [ 54 , 55 ]. Finally, we included the FTO gene, which codifies an alpha-ketoglutarate dependent dioxygenase and is one of the genes most strongly related with metabolic syndrome and obesity traits [ 56 , 57 ] and risk for type 2 diabetes (T2D) [ 58 ].…”