Association of drinking behaviors with TXNIP DNA methylation levels in leukocytes among the general Japanese population

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

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


Background: Thioredoxin-interacting protein (TXNIP) controls the cellular redox balance by binding to and inhibiting the expression and function of thioredoxin. DNA methylation of the TXNIP gene is involved in the regulation of TXNIP mRNA expression. Changes in TXNIP DNA methylation levels are associated with the development of various diseases such as type 2 diabetes mellitus (T2DM). However, few studies have focused on the influence of lifestyle factors such as alcohol intake on TXNIP DNA methylation. Objectives: This research examines the association of drinking behaviors with TXNIP DNA methylation levels in the general Japanese population. Methods: We conducted a cross-sectional study of 404 subjects (176 males and 228 females) who were divided into non-, moderate and heavy drinkers based on self-reported drinking behaviors. TXNIP DNA methylation levels in leukocytes were determined using a pyrosequencing assay. Results: The mean TXNIP DNA methylation level in heavy drinkers (74.2%) was significantly lower than that in non- and moderate drinkers (non: 77.7%, p < .001; moderate: 76.6%, p = .011). Multivariable linear regression analysis showed that log-transformed values of daily (b = −1.34; p < .001) and cumulative (b = −1.06; p = .001) alcohol consumption were associated with decreased TXNIP DNA methylation levels. Conclusion: TXNIP DNA methylation levels in heavy drinkers was lower than in non- and- moderate drinkers. Decreased TXNIP DNA methylation level increases the expression of TXNIP and elevates the risk of developing of diseases such as T2DM. Therefore, decreasing alcohol use in heavy drinkers may lessen the likelihood of some alcohol-related illnesses moderated through TXNIP DNA methylation.

Original languageEnglish
Pages (from-to)302-310
Number of pages9
JournalAmerican Journal of Drug and Alcohol Abuse
Issue number3
Publication statusPublished - 2022

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Clinical Psychology
  • Psychiatry and Mental health


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