Association of smoking habits withTXNIPDNA methylation levels in leukocytes among general Japanese population

Thioredoxin-interacting protein (TXNIP) inhibits the activity of thioredoxin (TXN), leading to increased oxidative stress. Expression of theTXNIPgene is regulated by DNA methylation. However, no study has reported the influence of lifestyle factors onTXNIPDNA methylation. Our goal was to determine the association between smoking habits andTXNIPDNA methylation levels in a Japanese population. We conducted a cross-sectional study of 417 subjects (180 males and 237 females) participating in a health examination. We used a pyrosequencing assay to determineTXNIPDNA methylation levels in leukocytes. The meanTXNIPDNA methylation level in current smokers (75.3%) was significantly lower than that in never and ex-smokers (never: 78.1%,p< 0.001; ex: 76.9%,p= 0.013). Multivariable logistic regression analyses showed that the OR forTXNIPDNA hypomethylation was significantly higher in current smokers than that in never smokers, and significantly higher in current smokers with years of smoking >= 35 and Brinkman Index >= 600 compared to that in non-smokers. In conclusion, we found that current smokers hadTXNIPDNA hypomethylation compared to never and ex-smokers. Moreover, long-term smoking and high smoking exposure also were associated withTXNIPDNA hypomethylation.