Thioredoxin-interacting protein (TXNIP) inhibits the activity of thioredoxin (TXN), leading to increased oxidative stress. Expression of the TXNIP gene is regulated by DNA methylation. However, no study has reported the influence of lifestyle factors on TXNIP DNA methylation. Our goal was to determine the association between smoking habits and TXNIP DNA 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 determine TXNIP DNA methylation levels in leukocytes. The mean TXNIP DNA 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 for TXNIP DNA 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 had TXNIP DNA hypomethylation compared to never and ex-smokers. Moreover, long-term smoking and high smoking exposure also were associated with TXNIP DNA hypomethylation.

硫氧还蛋白相互作用蛋白（TXNIP）抑制了硫氧还蛋白（TXN）的活性，导致氧化应激增加。所述的表达TXNIP基因由DNA甲基化调节。但是，尚无研究报道生活方式因素对TXNIP DNA甲基化的影响。我们的目标是确定日本人吸烟习惯与TXNIP DNA甲基化水平之间的关联。我们对参与健康检查的417位受试者（180位男性和237位女性）进行了横断面研究。我们使用了焦磷酸测序法来测定白细胞中的TXNIP DNA甲基化水平。平均TXNIP目前吸烟者的DNA甲基化水平（75.3％）显着低于从未吸烟者和前吸烟者（从未：78.1％，p <0.001；例如：76.9％，p = 0.013）。多变量logistic回归分析显示，当前吸烟者的TXNIP DNA低甲基化OR显着高于从未吸烟者，而吸烟年数≥35和Brinkman Index≥600的当前吸烟者与非吸烟者相比显着更高。总之，我们发现，与从不吸烟者和前吸烟者相比，当前吸烟者的TXNIP DNA甲基化程度较低。此外，长期吸烟和大量吸烟也与TXNIP DNA甲基化不足有关。