Interaction effect of genetic polymorphisms in glucokinase (GCK) and glucokinase regulatory protein (GCKR) on metabolic traits in healthy Chinese adults and adolescents.
OBJECTIVE
Recent studies in European populations have reported a reciprocal association of glucokinase regulatory protein (GCKR) gene with triglyceride versus fasting plasma glucose (FPG) levels and type 2 diabetes risk. GCKR is a rate-limiting factor of glucokinase (GCK), which functions as a key glycolytic enzyme for maintaining glucose homeostasis. We examined the associations of two common genetic polymorphisms of GCKR and GCK with metabolic traits in healthy Chinese adults and adolescents.


METHODS
Two single nucleotide polymorphisms (SNPs), rs780094 at GCKR and rs1799884 at GCK, were genotyped in 600 healthy adults and 986 healthy adolescents. The associations of these SNPs with metabolic traits were assessed by linear regression adjusted for age, sex, and/or BMI. We also tested for the epistasis between these two SNPs and performed a meta-analysis among European and Asian populations.


RESULTS
The T-allele of GCKR rs780094 was associated with increased triglycerides (P = 5.4 x 10(-7)), while the A-allele of GCK rs1799884 was associated with higher FPG (P = 3.1 x 10(-7)). A novel interaction effect between the two SNPs on FPG was also observed (P = 0.0025). Meta-analyses strongly supported the additive effects of the two SNPs on FPG and triglycerides, respectively. CONCLUSIONS;- In support of the intimate relationship between glucose and lipid metabolisms, GCKR and GCK genetic polymorphisms interact to increase FPG in healthy adults and adolescents. These risk alleles may contribute to increased diabetes risk in subjects who harbor other genetic or environmental/lifestyle risk factors.
Tam
Claudia H T
CH
Department of Medicine and Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China.
Ma
Ronald C W
RC
So
Wing Yee
WY
Wang
Ying
Y
Lam
Vincent K L
VK
Germer
Soren
S
Martin
Mitchell
M
Chan
Juliana C N
JC
Ng
Maggie C Y
MC
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D015992:Body Mass Index; D002681:China; D002784:Cholesterol / Q000097:blood; D005260:Female; D005941:Glucokinase / Q000235:genetics; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D008660:Metabolism / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D014280:Triglycerides / Q000097:blood
D048868:Adaptor Proteins, Signal Transducing; D001786:Blood Glucose; C485100:GCKR protein, human; D008055:Lipids; D014280:Triglycerides; D002784:Cholesterol; D005941:Glucokinase