Consumption of a Mediterranean diet (MD) and genetic variation in the glucokinase regulatory protein (GCKR) gene have been reported to be associated with TAG and glucose metabolism. It is uncertain whether there is any interaction between these factors. Therefore, the aims of the present study were to test the association of adherence to a MD and rs780094 (G>A) SNP in the GCKR gene with the markers of cardiometabolic risk, and to investigate the interaction between genetic variation and MD adherence. We studied 20 986 individuals from the European Prospective Investigation into Cancer (EPIC)-Norfolk study. The relative Mediterranean Diet Score (rMED: range 0–18) was used to assess MD adherence. Linear regression was used to estimate the association between the rMED, genotype and cardiometabolic continuous traits, adjusting for potential confounders. In adjusted analyses, we observed independent associations of MD adherence and genotype with cardiometabolic risk, with the highest risk group (AA genotype; lowest rMED) having higher concentrations of TAG, total cholesterol and apoB (12·5, 2·3 and 3·1 %, respectively) v. those at the lowest risk (GG genotype; highest rMED). However, the associations of MD adherence with metabolic markers did not differ by genotype, with no significant gene–diet interactions for lipids or for glycated Hb. In conclusion, we found independent associations of the rMED and of the GCKR genotype with cardiometabolic profile, but found no evidence of interaction between them.

The SNP rs1260326 (P446L) and rs1799884 ( − 30G>A) for the glucokinase regulatory protein (GCKR) and glucokinase (GCK) genes, respectively, have been associated with opposing effects on TAG and glucose concentrations. However, their genetic modulation by diet (dietary patterns or foods) remains to be investigated. We studied 945 high-cardiovascular risk subjects aged 67 (sd 6) years who participated in the PREvención con DIeta MEDiterránea-Valencia Study. Demographic, clinical, biochemical and genetic data were obtained. Adherence to the Mediterranean diet (MD) and food intake were measured by validated questionnaires. Carriers of the L allele of GKCR had significantly higher TAG concentrations (PP: 1·34 (sd 0·05) mmol/l v. PL+LL: 1·54 (sd 0·03) mmol/l; P= 0·014) and LL carriers had lower glucose concentrations (PL+PP: 6·85 (sd 0·08) mmol/l v. LL: 6·40 (sd 0·16) mmol/l; P= 0·032) after multivariate adjustment. Conversely, homozygous subjects for the variant allele (A) in the GCK gene had significantly lower TAG (GG+GA: 1·48 (sd 0·03) mmol/l v. AA: 1·17 (sd 0·18) mmol/l; P= 0·033) and a higher risk of diabetes (OR 3·3, 95 % CI 1·2, 9·2). Combined effects for both SNP increased TAG concentrations by 37 % (P= 0·033). Adherence to the MD modulated the effects of GCKR polymorphism on TAG: subjects with genetic risk had lower TAG (L-allele carriers; PP: 1·48 (sd 0·14) mmol/l v. PL+LL: 1·51 (sd 0·08) mmol/l; P= 0·917) compared with those with a higher adherence. Analysis of the joint effects of the GCKR and individual food items identified significant associations (olive oil (P= 0·035), vegetables (P= 0·012), red meat (P= 0·017), butter (P= 0·039), sweetened carbonated beverages (P= 0·036) and nuts (P= 0·038)). In conclusion, we found that rs1260326 (GCKR) is significantly associated with higher TAG concentrations, but is modulated by adherence to the MD.