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

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 studi...

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Main Authors: 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
Format: Article
Language:English
Published: The Japan Endocrine Society 2024-06-01
Series:Endocrine Journal
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Online Access:https://www.jstage.jst.go.jp/article/endocrj/71/6/71_EJ23-0629/_html/-char/en
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author 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_facet 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_sort Keisuke Maeda
collection DOAJ
description 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.
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spelling doaj-art-c887e932ac4a41ebb7551cade7f5237d2025-01-22T05:07:43ZengThe Japan Endocrine SocietyEndocrine Journal1348-45402024-06-0171659360110.1507/endocrj.EJ23-0629endocrjAssociation between DNA methylation levels of thioredoxin-interacting protein (TXNIP) and changes in glycemic traits: a longitudinal population-based studyKeisuke Maeda0Ryosuke Fujii1Hiroya Yamada2Eiji Munetsuna3Mirai Yamazaki4Yoshitaka Ando5Genki Mizuno6Hiroaki Ishikawa7Koji Ohashi8Yoshiki Tsuboi9Yuji Hattori10Yuya Ishihara11Nobuyuki Hamajima12Shuji Hashimoto13Koji Suzuki14Department of Clinical Physiology, Fujita Health University School of Medical Sciences, Toyoake 470-1192, JapanDepartment of Preventive Medical Sciences, Fujita Health University School of Medical Sciences, Toyoake 470-1192, JapanDepartment of Hygiene, Fujita Health University School of Medicine, Toyoake 470-1192, JapanDepartment of Biochemistry, Fujita Health University School of Medicine, Toyoake 470-1192, JapanDepartment of Medical Technology, Kagawa Prefectural University of Health Sciences, Takamatsu 761-0123, JapanDepartment of Biomedical and Analytical Sciences, Fujita Health University School of Medical Sciences, Toyoake 470-1192, JapanDepartment of Medical Technology, Tokyo University of Technology School of Health Sciences, Tokyo 144-8535, JapanDepartment of Biomedical and Analytical Sciences, Fujita Health University School of Medical Sciences, Toyoake 470-1192, JapanDepartment of Biomedical and Analytical Sciences, Fujita Health University School of Medical Sciences, Toyoake 470-1192, JapanDepartment of Preventive Medical Sciences, Fujita Health University School of Medical Sciences, Toyoake 470-1192, JapanDepartment of Preventive Medical Sciences, Fujita Health University School of Medical Sciences, Toyoake 470-1192, JapanDepartment of Preventive Medical Sciences, Fujita Health University School of Medical Sciences, Toyoake 470-1192, JapanDepartment of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya 466-8550, JapanDepartment of Hygiene, Fujita Health University School of Medicine, Toyoake 470-1192, JapanDepartment of Preventive Medical Sciences, Fujita Health University School of Medical Sciences, Toyoake 470-1192, JapanThioredoxin-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.https://www.jstage.jst.go.jp/article/endocrj/71/6/71_EJ23-0629/_html/-char/endna methylation (dnam)thioredoxin-interacting protein (txnip)glucosehemoglobin a1c (hba1c)type 2 diabetes (t2dm)
spellingShingle 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
Association between DNA methylation levels of thioredoxin-interacting protein (TXNIP) and changes in glycemic traits: a longitudinal population-based study
Endocrine Journal
dna methylation (dnam)
thioredoxin-interacting protein (txnip)
glucose
hemoglobin a1c (hba1c)
type 2 diabetes (t2dm)
title Association between DNA methylation levels of thioredoxin-interacting protein (TXNIP) and changes in glycemic traits: a longitudinal population-based study
title_full Association between DNA methylation levels of thioredoxin-interacting protein (TXNIP) and changes in glycemic traits: a longitudinal population-based study
title_fullStr Association between DNA methylation levels of thioredoxin-interacting protein (TXNIP) and changes in glycemic traits: a longitudinal population-based study
title_full_unstemmed Association between DNA methylation levels of thioredoxin-interacting protein (TXNIP) and changes in glycemic traits: a longitudinal population-based study
title_short Association between DNA methylation levels of thioredoxin-interacting protein (TXNIP) and changes in glycemic traits: a longitudinal population-based study
title_sort association between dna methylation levels of thioredoxin interacting protein txnip and changes in glycemic traits a longitudinal population based study
topic dna methylation (dnam)
thioredoxin-interacting protein (txnip)
glucose
hemoglobin a1c (hba1c)
type 2 diabetes (t2dm)
url https://www.jstage.jst.go.jp/article/endocrj/71/6/71_EJ23-0629/_html/-char/en
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