title: Discrete associations of the GCKR variant with metabolic risk in a Chinese population: longitudinal change analysis.
abstract: OBJECTIVE
  Glucokinase regulatory protein gene (GCKR) variant rs780092 is a novel genetic variant associated with serum triacylglycerol (TG) identified in a genome-wide association study in East Asians. We aimed to investigate associations of rs780092 with incident type 2 diabetes and dyslipidaemia, and the longitudinal changes in glucose and lipid levels.
  
  
  METHODS
  A community-based prospective cohort study was conducted at baseline in 2008, including 5,613 non-diabetic participants (37% male, mean age 57.6 years) with 5 years of follow-up. Blood glucose and lipid was measured at baseline and follow-up.
  
  
  RESULTS
  Each rs780092 T-allele was associated with a 17% lower risk of incident type 2 diabetes (HR 0.83 [95% CI 0.73, 0.95]) and 36% higher risk of incident hypertriacylglycerolaemia (OR 1.36 [95% CI 1.08, 1.72]), after adjustment for baseline fasting glucose and TG and other confounders. The T-allele was associated with a 5 year increasing level of log10 TG (β ± SE, 0.01 ± 0.004, p = 0.005). Mediation analysis showed that both baseline TG and the 5 year increase in log10 TG were significant mediators in the associations of rs780092 with risk of diabetes. The risk of incident type 2 diabetes associated with 1 SD increase in total and LDL-cholesterol was 35% and 22% lower in TT carriers compared with CC carriers, respectively (both p for interaction ≤ 0.04).
  
  
  CONCLUSIONS
  The GCKR rs780092 variant showed opposite-directional associations with type 2 diabetes and hypertriacylglycerolaemia in a Chinese population. Both baseline level and 5 year change in serum TG were mediators of the association between the genetic variant and type 2 diabetes.
authors.affiliation: State Key Laboratory of Medical Genomics, Key Laboratory for Endocrine and Metabolic Diseases of the Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai, 200025, China.
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Medical Genomics, Key Laboratory for Endocrine and Metabolic Diseases of the Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai, 200025, China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Lv
authors.affiliation: Department of Biomedical Engineering, Medical Systems Biology Research Center, Tsinghua University School of Medicine, 18 Life Science Park Road, Beijing, 100084, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Medical Genomics, Key Laboratory for Endocrine and Metabolic Diseases of the Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai, 200025, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Medical Genomics, Key Laboratory for Endocrine and Metabolic Diseases of the Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai, 200025, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Medical Genomics, Key Laboratory for Endocrine and Metabolic Diseases of the Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai, 200025, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Medical Genomics, Key Laboratory for Endocrine and Metabolic Diseases of the Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai, 200025, China.
authors.forename: Kui
authors.initials: K
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Medical Genomics, Key Laboratory for Endocrine and Metabolic Diseases of the Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai, 200025, China.
authors.forename: Po
authors.initials: P
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medical Genomics, Key Laboratory for Endocrine and Metabolic Diseases of the Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai, 200025, China.
authors.forename: Weiqing
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Qi
authors.affiliation: State Key Laboratory of Medical Genomics, Key Laboratory for Endocrine and Metabolic Diseases of the Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. byf10784@rjh.com.cn.|Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. byf10784@rjh.com.cn.|Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai, 200025, China. byf10784@rjh.com.cn.
authors.forename: Yufang
authors.initials: Y
authors.lastname: Bi
authors.affiliation: Department of Biomedical Engineering, Medical Systems Biology Research Center, Tsinghua University School of Medicine, 18 Life Science Park Road, Beijing, 100084, China. ymsun@capitalbio.com.|National Engineering Research Center for Beijing Biochip Technology, Beijing, China. ymsun@capitalbio.com.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Medical Genomics, Key Laboratory for Endocrine and Metabolic Diseases of the Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai, 200025, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Ning
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000368:Aged; D044466:Asian People / Q000235:genetics / Q000706:statistics & numerical data; D002681:China / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D050171:Dyslipidemias / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C485100:GCKR protein, human
keywords: GCKR; Single-nucleotide polymorphism; Triacylglycerol; Type 2 diabetes