GCK gene-body hypomethylation is associated with the risk of coronary heart disease.
OBJECTIVE
Glucokinase encoded by GCK is a key enzyme that facilitates phosphorylation of glucose to glucose-6-phosphate. Variants of GCK gene were shown to be associated with type 2 diabetes (T2D) and coronary heart disease (CHD). The goal of this study was to investigate the contribution of GCK gene-body methylation to the risk of CHD.


METHODS
36 patients (18 males and 18 females) and 36 age- and sex-matched controls were collected for the current methylation research. DNA methylation level of the CpG island (CGI) region on the GCK gene-body was measured through the sodium bisulfite DNA conversion and pyrosequencing technology.


RESULTS
Our results indicated that CHD cases have a much lower methylation level (49.77 ± 6.43%) compared with controls (54.47 ± 7.65%, P = 0.018). In addition, GCK gene-body methylation was found to be positively associated with aging in controls (r = 0.443, P = 0.010).


CONCLUSIONS
Our study indicated that the hypomethylation of GCK gene-body was significantly associated with the risk of CHD. Aging correlates with an elevation of GCK methylation in healthy controls.
Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, Zhejiang 315211, China ; The Affiliated Hospital, Ningbo University School of Medicine, Ningbo, Zhejiang 315211, China ; Ningbo Medical Center Lihuili Hospital, Ningbo University School of Medicine, Ningbo, Zhejiang 315041, China.
Limin
L
Xu
Ningbo Medical Center Lihuili Hospital, Ningbo University School of Medicine, Ningbo, Zhejiang 315041, China.
Dawei
D
Zheng
Bank of Blood Products, Ningbo No. 2 Hospital, Ningbo, Zhejiang 315010, China.
Lingyan
L
Wang
Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, Zhejiang 315211, China ; The Affiliated Hospital, Ningbo University School of Medicine, Ningbo, Zhejiang 315211, China.
Danjie
D
Jiang
Yinzhou People's Hospital, Ningbo University School of Medicine, Ningbo, Zhejiang 315040, China.
Haibo
H
Liu
Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, Zhejiang 315211, China ; The Affiliated Hospital, Ningbo University School of Medicine, Ningbo, Zhejiang 315211, China.
Leiting
L
Xu
Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, Zhejiang 315211, China ; The Affiliated Hospital, Ningbo University School of Medicine, Ningbo, Zhejiang 315211, China.
Qi
Q
Liao
Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, Zhejiang 315211, China ; The Affiliated Hospital, Ningbo University School of Medicine, Ningbo, Zhejiang 315211, China.
Lina
L
Zhang
Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, Zhejiang 315211, China ; The Affiliated Hospital, Ningbo University School of Medicine, Ningbo, Zhejiang 315211, China.
Panpan
P
Liu
Ningbo Medical Center Lihuili Hospital, Ningbo University School of Medicine, Ningbo, Zhejiang 315041, China.
Xinbao
X
Shi
Ningbo Medical Center Lihuili Hospital, Ningbo University School of Medicine, Ningbo, Zhejiang 315041, China.
Zhaoyang
Z
Wang
Ningbo Medical Center Lihuili Hospital, Ningbo University School of Medicine, Ningbo, Zhejiang 315041, China.
Lebo
L
Sun
Ningbo Medical Center Lihuili Hospital, Ningbo University School of Medicine, Ningbo, Zhejiang 315041, China.
Qingyun
Q
Zhou
Ningbo Medical Center Lihuili Hospital, Ningbo University School of Medicine, Ningbo, Zhejiang 315041, China.
Ni
N
Li
Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, Zhejiang 315211, China ; The Affiliated Hospital, Ningbo University School of Medicine, Ningbo, Zhejiang 315211, China.
Yi
Y
Huang
Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, Zhejiang 315211, China ; The Affiliated Hospital, Ningbo University School of Medicine, Ningbo, Zhejiang 315211, China.
Yanping
Y
Le
The Affiliated Hospital, Ningbo University School of Medicine, Ningbo, Zhejiang 315211, China.
Meng
M
Ye
Ningbo Medical Center Lihuili Hospital, Ningbo University School of Medicine, Ningbo, Zhejiang 315041, China.
Guofeng
G
Shao
Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, Zhejiang 315211, China ; The Affiliated Hospital, Ningbo University School of Medicine, Ningbo, Zhejiang 315211, China.
Shiwei
0000-0001-7682-2877
S
Duan
D016022:Case-Control Studies; D003327:Coronary Disease / Q000201:enzymology* / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005941:Glucokinase / Q000235:genetics*; D006801:Humans; D008297:Male; D012307:Risk Factors
D005941:Glucokinase