title: Elevated CpG island methylation of GCK gene predicts the risk of type 2 diabetes in Chinese males.
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).
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Linlin
authors.initials: L
authors.lastname: Tang
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.
authors.forename: Huadan
authors.initials: H
authors.lastname: Ye
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.
authors.forename: Qingxiao
authors.initials: Q
authors.lastname: Hong
authors.affiliation: Bank of Blood Products, Ningbo No.2 Hospital, Ningbo, Zhejiang 315010, China.
authors.forename: Lingyan
authors.initials: L
authors.lastname: Wang
authors.affiliation: The Affiliated Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang 315000, China; Diabetes Center, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.
authors.forename: Qinwen
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Section of Endocrinology, Pritzker School of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Wang
authors.affiliation: The Affiliated Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang 315000, China; Diabetes Center, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.
authors.forename: Leiting
authors.initials: L
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Shizhong
authors.initials: S
authors.lastname: Bu
authors.affiliation: 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.
authors.forename: Lina
authors.initials: L
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Jia
authors.initials: J
authors.lastname: Cheng
authors.affiliation: 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.
authors.forename: Panpan
authors.initials: P
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Le
authors.affiliation: The Affiliated Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang 315000, China. Electronic address: dryemeng@yahoo.com.cn.
authors.forename: Meng
authors.initials: M
authors.lastname: Ye
authors.affiliation: The Affiliated Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang 315000, China. Electronic address: nbmyf@msn.com.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Mai
authors.affiliation: 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.
authors.forename: Shiwei
authors.initials: S
authors.lastname: Duan
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D002681:China; D018899:CpG Islands; D019175:DNA Methylation; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D000081410:Germinal Center Kinases; D006593:Hexokinase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012737:Sex Factors
chemical_list: D000081410:Germinal Center Kinases; D006593:Hexokinase; D017346:Protein Serine-Threonine Kinases
keywords: CpG island; DNA methylation; GCK; Gender; Type 2 diabetes