To estimate the T2DM incidence with DNA methylation of thioredoxin-interacting protein gene (TXNIP) and its interaction with environmental factors.This case-control study included 286 incident T2DM cases and 286 non-T2DM controls matched by sex, age, marital status, race, and residence village nested in the Rural Chinese Cohort Study. A conditional logistic regression model was used to estimate the association of DNA methylation at TXNIP with T2DM risk. Also, multifactor dimensionality reduction (MDR) and classification and regression tree (CART) analyses were used to investigate the interaction between TXNIP methylation and environmental risk factors.Methylation levels of all five CpG loci at TXNIP were significantly lower in T2DM than controls (all P < 0.001). With increasing methylation level, risk of T2DM was significantly decreased (odds ratio 95% confidence interval 0.80, 0.69-0.94 for CpG1; 0.80, 0.69-0.93 for CpG2; 0.70, 0.56-0.88 for CpG3; 0.78, 0.66-0.92 for CpG4; and 0.76; 0.60-0.97 for CpG5). Additionally, the essential interactions among TXNIP methylation, obesity, and hypertriglyceridemia were identified by CART and MDR analyses. On logistic regression analysis, the risk of T2DM was reduced with terminal node 5 (CpG3 methylation ≥72%, non-obesity, normal TG level, and CpG4 methylation ≥83%) vs terminal node 1 (CpG3 methylation <72%) (odds ratio 95% confidence interval 0.20, 0.10-0.40).TXNIP methylation was associated with T2DM incidence in a Chinese population. Interaction between TXNIP methylation and environmental factors may influence T2DM risk and needs more investigation. This article is protected by copyright. All rights reserved.
