Associations of <i>apolipoprotein A5 (APOA5), glucokinase (GCK)</i> and <i>glucokinase regulatory protein (GCKR)</i> polymorphisms and lifestyle factors with the risk of dyslipidemia and dysglycemia in Japanese — a cross-sectional data from the J-MICC Study

Abstract

IN THE rEcENT dEcadEs, sedentary lifestyles became more and more common, and lifestyle-related Associations of apolipoprotein A5 (APOA5), glucokinase (GCK)and glucokinase regulatory protein (GCKR) polymorphisms and lifestyle factors with the risk of dyslipidemia and dysglycemia in Japanese -a cross-sectional data from the J-MICC Study 770-8503, Japan 11) Center for Genomic Medicine, RIKEN, Yokohama 230-0045, Japanabstract. This study examined the associations of the APOA5 T-1131C (rs662799), G553T (Cys185Gly, rs2075291), GCK G-30A (rs1799884), GCKR A/G at intron 16 (rs780094) and T1403C (Leu446Pro, rs1260326) polymorphisms with serum lipid and glucose levels in Japanese, considering lifestyle factors. Study subjects were 2,191 participants (aged 35-69 years, 1,159 males) enrolled in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. Dyslipidemia was defined as fasting serum triglycerides (FTG) ≥ 150 mg/dL and/or HDL-cholesterol (HDL-C) < 40 mg/dL, while dysglycemia was as fasting blood sugar (FBS) ≥ 110 mg/dL. When those with APOA5 -1131 T/T or 553 G/G were defined as references, those with APOA5 -1131 T/C, C/C or 553 G/T, T/T demonstrated significantly elevated risk of dyslipidemia (age-and sex-adjusted odds ratio: 1.77 [95% confidence interval:1.39-2.27], 3.35 [2.41-4.65], 2.23 [1.64-3.02] and 13.78 [3.44-55.18], respectively). Evaluation of FTG, HDL-C or FBS levels according to the genotype revealed that FTG and HDL-C levels were significantly associated with the APOA5 T-1131C and G553T polymorphisms, FTG with the GCKR rs780094 and rs1260326 polymorphisms, and FBS with the GCKR rs780094 and rs1260326 polymorphisms. Moreover, a significant positive interaction between APOA5 553 G/T+T/T genotypes and fat intake ≥ 25% of total energy for the risk of dyslipidemia was observed. Our crosssectional study confirmed the essential roles of the polymorphisms of the APOA5, GCK and GCKR in the lipid or glucose metabolism disorders, and suggested the importance of fat intake control in the individualized prevention of dyslipidemia.

Functional Variants of Lipid Level Modifier MLXIPL, GCKR, GALNT2, CILP2, ANGPTL3 and TRIB1 Genes in Healthy Roma and Hungarian Populations

“…Worldwide, the role of serum triglycerides and total cholesterol in relation to development of several diseases, especially cardio-and cerebrovascular diseases, metabolic syndrome and diabetes mellitus is extensively investigated [4,10,11,30,[35][36][37][38]. In the past few years, several studies described new genetic polymorphisms which have an effect on triglyceride level alteration, like GCKR and APOA5 variants [11,30,[35][36][37][38].…”

“…In the past few years, several studies described new genetic polymorphisms which have an effect on triglyceride level alteration, like GCKR and APOA5 variants [11,30,[35][36][37][38]. The mechanism of glucokinase enzyme of the liver is under control by glucokinase regulatory protein (GCKR), which enzyme has a dominant glucose phosphorylase role of the liver and of the pancreatic β-cells in the glucose homeostasis of the blood [39][40][41].…”

The dietary monounsaturated to saturated fatty acid ratio modulates the genetic effects of GCKR on serum lipid levels in children

“…In addition, the effects of the interaction between GCKR genetic variants and lifestyle factors, including dietary factors, on glucose metabolism, dyslipidemia, and cardiometabolic traits have recently been investigated [14], [15], [16] and [17]. Since dietary unsaturated fatty acid (UFA) intake results in a healthy blood lipid profile and modulates blood pressure and glucose levels, metabolic disorders possibly could be regulated through unsaturated fatty acid preferential oxidation of unsaturated fatty acid and metabolism of blood lipids [18].…”

Genetic Diagnosis via Whole Exome Sequencing in Taiwanese Patients with Hypertriglyceridemia

“…APOA5 indirectly regulates TG metabolism by stimulating the lipoprotein lipase (LPL) activity, which increases the rate of LPL-mediated TG 30) . In previous genotyping and haplotyping studies, the APOA5 gene was reported to be associated with an elevated TG level; however, the clinical significance and prevalence varied among different ethnicities [31][32][33][34][35][36][37][38][39] . In Taiwan, two haplotypes of APOA5 (rs662799 and rs2075291) have been found to be closely related to HTG 39) .…”