Association between DNA methylation levels of thioredoxin-interacting protein (TXNIP) and changes in glycemic traits: a longitudinal population-based study

Keisuke Maeda; Ryosuke Fujii; Hiroya Yamada; Eiji Munetsuna; Mirai Yamazaki; Yoshitaka Ando; Genki Mizuno; Hiroaki Ishikawa; Koji Ohashi; Yoshiki Tsuboi; Yuji Hattori; Yuya Ishihara; Nobuyuki Hamajima; Shuji Hashimoto; Koji Suzuki

doi:10.1507/endocrj.EJ23-0629

Association between DNA methylation levels of thioredoxin-interacting protein (TXNIP) and changes in glycemic traits: a longitudinal population-based study

Keisuke Maeda ^†, Ryosuke Fujii ^†, Hiroya Yamada, Eiji Munetsuna, Mirai Yamazaki, Yoshitaka Ando, Genki Mizuno, Hiroaki Ishikawa, Koji Ohashi, Yoshiki Tsuboi, Yuji Hattori, Yuya Ishihara, Nobuyuki Hamajima, Shuji Hashimoto, Koji Suzuki

Author information

Keisuke Maeda ^†
https://orcid.org/0000-0001-8916-2687
Department of Clinical Physiology, Fujita Health University School of Medical Sciences, Toyoake 470-1192, Japan
Ryosuke Fujii ^†
https://orcid.org/0000-0003-1730-2059
Department of Preventive Medical Sciences, Fujita Health University School of Medical Sciences, Toyoake 470-1192, Japan
Institute for Biomedicine (affiliated to the University of Lübeck), Eurac Research, Bolzano/Bozen 39100, Italy
Hiroya Yamada
Department of Hygiene, Fujita Health University School of Medicine, Toyoake 470-1192, Japan
Eiji Munetsuna
Department of Biochemistry, Fujita Health University School of Medicine, Toyoake 470-1192, Japan
Mirai Yamazaki
Department of Medical Technology, Kagawa Prefectural University of Health Sciences, Takamatsu 761-0123, Japan
Yoshitaka Ando
Department of Biomedical and Analytical Sciences, Fujita Health University School of Medical Sciences, Toyoake 470-1192, Japan
Genki Mizuno
Department of Medical Technology, Tokyo University of Technology School of Health Sciences, Tokyo 144-8535, Japan
Hiroaki Ishikawa
Department of Biomedical and Analytical Sciences, Fujita Health University School of Medical Sciences, Toyoake 470-1192, Japan
Koji Ohashi
Department of Biomedical and Analytical Sciences, Fujita Health University School of Medical Sciences, Toyoake 470-1192, Japan
Yoshiki Tsuboi
https://orcid.org/0000-0001-8145-3949
Department of Preventive Medical Sciences, Fujita Health University School of Medical Sciences, Toyoake 470-1192, Japan
Yuji Hattori
Department of Preventive Medical Sciences, Fujita Health University School of Medical Sciences, Toyoake 470-1192, Japan
Yuya Ishihara
Department of Preventive Medical Sciences, Fujita Health University School of Medical Sciences, Toyoake 470-1192, Japan
Nobuyuki Hamajima
Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
Shuji Hashimoto
Department of Hygiene, Fujita Health University School of Medicine, Toyoake 470-1192, Japan
Koji Suzuki Corresponding author
https://orcid.org/0000-0002-3235-9558
Department of Preventive Medical Sciences, Fujita Health University School of Medical Sciences, Toyoake 470-1192, Japan
Author contributions

†These authors contributed equally: Keisuke Maeda, Ryosuke Fujii

Keywords: DNA methylation (DNAm), Thioredoxin-interacting protein (TXNIP), Glucose, Hemoglobin A1c (HbA1c), Type 2 diabetes (T2DM)

JOURNAL OPEN ACCESS Advance online publication
Supplementary material

Article ID: EJ23-0629

DOI https://doi.org/10.1507/endocrj.EJ23-0629

Details

Abstract

Thioredoxin-interacting protein (TXNIP) plays an important role in glucose metabolism, and its expression is regulated by DNA methylation (DNAm). Although the association between TXNIP DNAm and type 2 diabetes mellitus has been demonstrated in studies with a cross-sectional design, prospective studies are needed. We therefore examined the association between TXNIP DNAm levels and longitudinal changes in glycemic traits by conducting a longitudinal study involving 169 subjects who underwent two health checkups in 2015 and 2019. We used a pyrosequencing assay to determine TXNIP DNAm levels in leukocytes (cg19693031). Logistic regression analyses were performed to assess the associations between dichotomized TXNIP DNAm levels and marked increases in glycemic traits. At four years, the TXNIP DNA hypomethylation group had a higher percentage of changes in fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) compared to those in the hypermethylation group. The adjusted odds ratios for FPG and HbA1c levels were significantly higher in the TXNIP DNA hypomethylation group than in the hypermethylation group. We found that TXNIP DNA hypomethylation at baseline was associated with a marked increase in glycemic traits. Leukocyte TXNIP DNAm status could potentially be used as an early biomarker for impaired glucose homeostasis.

Corresponding author

Register with J-STAGE for free!