Early gene-diet interaction between glucokinase regulatory protein (GCKR) polymorphism, vegetable and fish intakes in modulating triglyceride levels in healthy adolescents

Background and aims: The benefits of dietary vegetable and fish consumptions on improving glucose and lipid metabolism have been well established. Recently, the T-allele of a common genetic variant rs780094 at glucokinase regulatory protein (GCKR) was reported to be associated with elevated triglyceride (TG) levels but reduced fasting plasma glucose (FPG) and type 2 diabetes risk. However, the dietary modulation on genetic risk is not clearly understood. Methods and results: A cohort of 2095 Chinese adolescents (mean age 15.6 +/- 2.0 years, 45.3% male) recruited from a population-based school survey for cardiovascular risk factor assessment, with dietary data including weekly vegetable and fish consumptions as well as clinical data were genotyped for the GCKR rs780094 polymorphism. In the linear regression analysis with adjustment for sex, age, body mass index, and socioeconomic status (school banding, paternal and maternal education levels), the frequency of vegetable intake per week was inversely associated with FPG (P = 0.044). Individuals with low fish intake generally had elevated TG levels but reduced TC, HDL-C and LDL-C (0.006 < P < 0.029). We also observed significant associations of the minor T-allele of GCKR rs780094 with decreased FPG (P = 0.013) and increased TG levels (P = 2.7 x 10(-8)). There were significant gene-diet interactions between rs780094 and vegetable consumption (P-interaction = 0.009), and between rs780094 and fish consumption (P-interaction = 0.031) in modulating TG levels. The T-allele of GCKR locus was associated with higher TG levels amongst individuals with >= 7 vegetable meals per week (P = 6.4 x 10(-9)), and among individuals with <7 fish meals per week (P = 0.020 and 7.0 x 10(-7) for 4-6 and <= 3 meals per week, respectively). High intake of vegetable exerted a reduction in TG levels only among CC genotype carriers (Ptrend = 0.020), while high intake of fish was associated with reduced TG levels only among TT genotype carriers (Ptrend = 0.026). Conclusions: In summary, our data indicated that the favorable associations of higher vegetable and fish intakes on TG levels are dependent on the genetic background of an individual. In particular, at-risk TT-genotype carriers of the GCKR variant may derive more benefits from a high fish intake, while the CC-genotype carriers may find further benefits from a high consumption of vegetable. (C) 2015 Elsevier B.V. All rights reserved.