Research Papers: Immunology:

Epigenetic regulation of HGK/MAP4K4 in T cells of type 2 diabetes patients

Huai-Chia Chuang _, Jun-Sing Wang, I-Te Lee, Wayne H-H. Sheu and Tse-Hua Tan

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Oncotarget. 2016; 7:10976-10989. https://doi.org/10.18632/oncotarget.7686

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Huai-Chia Chuang1, Jun-Sing Wang2, I-Te Lee2, Wayne H-H. Sheu2,3,* and Tse-Hua Tan1,4,*

1 Immunology Research Center, National Health Research Institutes, Zhunan, Taiwan

2 Division of Endocrinology and Metabolism, Taichung Veterans General Hospital, Taichung, Taiwan

3 Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan

4 Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA

* These authors have contributed equally to this work

Correspondence to:

Tse-Hua Tan, email:

Wayne H-H. Sheu, email:

Keywords: type 2 diabetes, HGK methylation, HGK downregulation, IL-6-producing T cells, Immunology and Microbiology Section, Immune response, Immunity

Received: October 15, 2015 Accepted: February 05, 2016 Published: February 24, 2016


Type 2 diabetes (T2D) is a complex and heterogeneous disease. Obesity increases the risk of obese T2D; but in Asia non-obese T2D is prevalent. The cause of non-obese T2D has remained elusive. We studied the potential involvement of HGK/MAP4K4 in T2D using clinical samples from newly diagnosed, drug-naïve patients and healthy controls. HGK levels fell and IL-6 levels increased in T cells from T2D patients. Frequencies of IL-6-producing T cells were correlated with glucose levels after glucose-tolerance tests (but not body mass index and waist circumference) and inversely correlated with HGK expression levels. Moreover, methylation frequencies of the HGK promoter were increased in T2D patients and correlated with glucose levels after glucose-tolerance tests. The correlation was independent of body mass index. Demethylation treatment increased HGK expression levels and reduced IL-6 production in T2D T cells. This report identifies HGK methylation/downregulation in T cells as a potential biomarker for non-obese T2D.

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