Interaction Effect of Genetic Polymorphisms in Glucokinase (GCK) and Glucokinase Regulatory Protein (GCKR) on Metabolic Traits in Healthy Chinese Adults and Adolescents
- Claudia H.T. Tam1,
- Ronald C.W. Ma1,
- Wing Yee So1,
- Ying Wang1,
- Vincent K.L. Lam1,
- Soren Germer2,
- Mitchell Martin2,
- Juliana C.N. Chan134 and
- Maggie C.Y. Ng1
- 1Department of Medicine and Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China
- 2Roche Pharmaceuticals, Nutley, New Jersey
- 3Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China
- 4Hong Kong Institute of Diabetes and Obesity, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China
- Corresponding author: Juliana C.N. Chan, jchan{at}cuhk.edu.hk
Abstract
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.
RESEARCH DESIGN AND 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 × 10−7), while the A-allele of GCK rs1799884 was associated with higher FPG (P = 3.1 × 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.
Footnotes
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Published ahead of print at http://diabetes.diabetesjournals.org on 10 December 2008.
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- Accepted December 5, 2008.
- Received September 16, 2008.
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