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

ABSTRACT

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.

KEYWORDS:

• Epigenetics
• DNA methylation
• thioredoxin-interacting protein
• drinking behavior
• alcohol use

Acknowledgements

The authors thank the participants and staff of the Health Examination Program for Residents of Yakumo, Hokkaido, Japan.

Disclosure statement

The authors report there are no competing interests to declare.

Additional information

Funding

This work was supported by the Japan Society for the Promotion of Science under Grants-in-Aid for Scientific Research [numbers 26293144, 17K09139, 16H06277, and 20K10515].