TY - JOUR
T1 - Genotype effects of glucokinase regulator on lipid profiles and glycemic status are modified by circulating calcium levels
T2 - results from the Korean Genome and Epidemiology Study
AU - Kim, Oh Yoen
AU - Kwak, So Young
AU - Lim, Hyunjung
AU - Shin, Min Jeong
N1 - Funding Information:
Bioresources for the study were provided by the National Biobank of Korea and the Centers for Disease Control and Prevention, Republic of Korea ( KBP-2016-009 ). This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology ( NRF-2015R1A2A1A15054758 ), by the Ministry of Education ( NRF-2018R1D1A1B07042376 ), and by the Bio & Medical Technology Development Program of the NRF funded by the Ministry of Science & ICT ( NRF-2012M3A9C4048761 ). The authors declare that there are no conflicts of interest.
Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/12
Y1 - 2018/12
N2 - Single nucleotide polymorphisms (SNPs) in the glucokinase regulator (GCKR) are associated with major cardiovascular risk factors (ie, lipid profile and glycemic status). Recently, GCKR was shown to be related to circulating calcium levels involved in lipid and glycemic controls. Therefore, we hypothesized that GCKR SNPs are associated with major cardiovascular risk factors in the Korean population, and the association is modified by circulating calcium levels. Epidemiological data and GCKR SNPs (rs780093T>C, rs780094 T>C, and rs1260326 T>C) were collected from a subset of Ansung-Ansan cohort in the Korean Genome and Epidemiology Study (n = 7815). Consistent with the results of previous studies, GCKR SNPs were significantly associated with decreased total cholesterol and triglyceride levels and increased glucose levels and insulin resistance. Minor C allele carriers, particularly CC homozygotes, had lower serum calcium levels than TT homozygotes for all 3 SNPs. Particularly, the effect of GCKR SNPs on total cholesterol, triglyceride, fasting glucose, and insulin resistance was apparent when serum calcium levels were in normal range (8.8-10.1 mg/dL). When serum calcium levels were high (≥10.2 mg/dL), CC homozygotes also had significantly lower triglyceride and higher fasting glucose than TT homozygotes. However, the associations were not observed when serum calcium levels were low (<8.8 mg/dL). In conclusion, GCKR SNPs are associated with lipid profiles and glycemic status in the Korean population, and the genetic effect is modified by basal circulating calcium levels, particularly in normal or high ranges. It provides important information for individualized prevention and management of cardiovascular risk associated with GCKR SNPs.
AB - Single nucleotide polymorphisms (SNPs) in the glucokinase regulator (GCKR) are associated with major cardiovascular risk factors (ie, lipid profile and glycemic status). Recently, GCKR was shown to be related to circulating calcium levels involved in lipid and glycemic controls. Therefore, we hypothesized that GCKR SNPs are associated with major cardiovascular risk factors in the Korean population, and the association is modified by circulating calcium levels. Epidemiological data and GCKR SNPs (rs780093T>C, rs780094 T>C, and rs1260326 T>C) were collected from a subset of Ansung-Ansan cohort in the Korean Genome and Epidemiology Study (n = 7815). Consistent with the results of previous studies, GCKR SNPs were significantly associated with decreased total cholesterol and triglyceride levels and increased glucose levels and insulin resistance. Minor C allele carriers, particularly CC homozygotes, had lower serum calcium levels than TT homozygotes for all 3 SNPs. Particularly, the effect of GCKR SNPs on total cholesterol, triglyceride, fasting glucose, and insulin resistance was apparent when serum calcium levels were in normal range (8.8-10.1 mg/dL). When serum calcium levels were high (≥10.2 mg/dL), CC homozygotes also had significantly lower triglyceride and higher fasting glucose than TT homozygotes. However, the associations were not observed when serum calcium levels were low (<8.8 mg/dL). In conclusion, GCKR SNPs are associated with lipid profiles and glycemic status in the Korean population, and the genetic effect is modified by basal circulating calcium levels, particularly in normal or high ranges. It provides important information for individualized prevention and management of cardiovascular risk associated with GCKR SNPs.
KW - Blood glucose
KW - Calcium
KW - Cardiovascular diseases
KW - Lipids
KW - Polymorphism
KW - Single nucleotide
UR - http://www.scopus.com/inward/record.url?scp=85054737457&partnerID=8YFLogxK
U2 - 10.1016/j.nutres.2018.09.008
DO - 10.1016/j.nutres.2018.09.008
M3 - Article
C2 - 30527264
AN - SCOPUS:85054737457
SN - 0271-5317
VL - 60
SP - 96
EP - 105
JO - Nutrition Research
JF - Nutrition Research
ER -