title: 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.
abstract: 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 cross-sectional 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.
authors.affiliation: Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan. a-hishi@med.nagoya-u.ac.jp
authors.forename: Asahi
authors.initials: A
authors.lastname: Hishida
authors.forename: Emi
authors.initials: E
authors.lastname: Morita
authors.forename: Mariko
authors.initials: M
authors.lastname: Naito
authors.forename: Rieko
authors.initials: R
authors.lastname: Okada
authors.forename: Kenji
authors.initials: K
authors.lastname: Wakai
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Nakamura
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Takashima
authors.forename: Sadao
authors.initials: S
authors.lastname: Suzuki
authors.forename: Toshiro
authors.initials: T
authors.lastname: Takezaki
authors.forename: Haruo
authors.initials: H
authors.lastname: Mikami
authors.forename: Keizo
authors.initials: K
authors.lastname: Ohnaka
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Uemura
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.forename: Hideo
authors.initials: H
authors.lastname: Tanaka
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hamajima
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000368:Aged; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A / Q000235:genetics*; D044466:Asian People / Q000235:genetics / Q000706:statistics & numerical data; D003430:Cross-Sectional Studies; D003627:Data Interpretation, Statistical; D004198:Disease Susceptibility; D050171:Dyslipidemias / Q000453:epidemiology / Q000208:ethnology / Q000209:etiology / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005941:Glucokinase / Q000235:genetics*; D044882:Glucose Metabolism Disorders / Q000453:epidemiology / Q000208:ethnology / Q000209:etiology / Q000235:genetics*; D006801:Humans; D008019:Life Style; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D012307:Risk Factors
chemical_list: C437704:APOA5 protein, human; D048868:Adaptor Proteins, Signal Transducing; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A; C485100:GCKR protein, human; D005941:Glucokinase