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. 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.
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.
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.