Elevated CpG island methylation of GCK gene predicts the risk of type 2 diabetes in Chinese males

Linlin Tang; Huadan Ye; Qingxiao Hong; Lingyan Wang; Qinwen Wang; Hongwei Wang; Leiting Xu; Shizhong Bu; Lina Zhang; Jia Cheng; Panpan Liu; Yanping Le; Meng Ye; Yifeng Mai; Shiwei Duan

doi:10.1016/j.gene.2014.06.062

Elevated CpG island methylation of GCK gene predicts the risk of type 2 diabetes in Chinese males

Gene. 2014 Sep 1;547(2):329-33. doi: 10.1016/j.gene.2014.06.062. Epub 2014 Jun 30.

Authors

Linlin Tang¹, Huadan Ye², Qingxiao Hong², Lingyan Wang³, Qinwen Wang⁴, Hongwei Wang⁵, Leiting Xu⁴, Shizhong Bu⁶, Lina Zhang⁶, Jia Cheng⁶, Panpan Liu⁶, Yanping Le⁶, Meng Ye⁷, Yifeng Mai⁸, Shiwei Duan⁹

Affiliations

¹ Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China; The Affiliated Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang 315000, China; Diabetes Center, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.
² Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.
³ Bank of Blood Products, Ningbo No.2 Hospital, Ningbo, Zhejiang 315010, China.
⁴ The Affiliated Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang 315000, China; Diabetes Center, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.
⁵ Section of Endocrinology, Pritzker School of Medicine, The University of Chicago, Chicago, IL 60637, USA.
⁶ Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China; Diabetes Center, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.
⁷ The Affiliated Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang 315000, China. Electronic address: dryemeng@yahoo.com.cn.
⁸ The Affiliated Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang 315000, China. Electronic address: nbmyf@msn.com.
⁹ Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China; The Affiliated Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang 315000, China; Diabetes Center, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China. Electronic address: duanshiwei@nbu.edu.cn.

PMID: 24992032
DOI: 10.1016/j.gene.2014.06.062

Abstract

Background: The GCK gene encodes hexokinase 4, which catalyzes the first step in most glucose metabolism pathways. The purpose of our study is to assess the contribution of GCK methylation to type 2 diabetes (T2D).

Methods and results: GCK methylation was evaluated in 48 T2D cases and 48 age- and gender-matched controls using the bisulphite pyrosequencing technology. Among the four CpG sites in the methylation assay, CpG4 and the other three CpGs (CpG1-3) were not in high correlation (r<0.5). Significantly elevated methylation levels of GCK CpG4 methylation were observed in T2D patients than in the healthy controls (P=0.004). A breakdown analysis by gender indicated that the association between CpG4 methylation and T2D was specific to males (P=0.002). It is intriguing that another significant male-specific association was also found between GCK CpG4 methylation and total cholesterol (TC) concentration (r=0.304, P=0.036).

Conclusion: Our results showed that elevated GCK CpG4 methylation might suggest a risk of T2D in Chinese males. Gender disparity in GCK CpG4 methylation might provide a clue to elaborate the pathogenesis of T2D.

Keywords: CpG island; DNA methylation; GCK; Gender; Type 2 diabetes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Case-Control Studies
China
CpG Islands*
DNA Methylation*
Diabetes Mellitus, Type 2 / genetics*
Female
Germinal Center Kinases
Hexokinase / genetics*
Humans
Male
Middle Aged
Protein Serine-Threonine Kinases / genetics*
Sex Factors

Substances

Germinal Center Kinases
Hexokinase
Protein Serine-Threonine Kinases