Open AccessTXNIP 低甲基化及其与肥胖和高甘油三酯血症的交互作用可增加2型糖尿病的风险:巢式病例对照研究
Author(s) -
Zhang Dongdong,
Cheng Cheng,
Cao Meng,
Wang Tieqiang,
Chen Xiaoliang,
Zhao Yang,
Wang Bingyuan,
Ren Yongcheng,
Liu Dechen,
Liu Leilei,
Chen Xu,
Liu Feiyan,
Zhou Qionggui,
Tian Gang,
Li Quanman,
Guo Chunmei,
Li Honghui,
Wang Jian,
Cheng Ruirong,
Hu Dongsheng,
Zhang Ming
Publication year - 2020
Publication title -
journal of diabetes
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.949
H-Index - 43
eISSN - 1753-0407
pISSN - 1753-0393
DOI - 10.1111/1753-0407.13021
Subject(s) - txnip , medicine , nested case control study , odds ratio , methylation , type 2 diabetes mellitus , dna methylation , hypertriglyceridemia , type 2 diabetes , endocrinology , oncology , diabetes mellitus , biology , triglyceride , genetics , gene , cholesterol , gene expression , oxidative stress , thioredoxin
Background This study aims to estimate type 2 diabetes mellitus (T2DM) incidence with DNA methylation of the thioredoxin‐interacting protein ( TXNIP ) gene and its interaction with environmental factors. Materials and Methods 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 gene 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. Results Methylation levels of all five CpG loci at TXNIP gene were significantly lower in T2DM than in controls (all P < .001). With increasing methylation level, risk of T2DM was significantly decreased (odds ratio, 95% CI 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%, nonobesity, normal triglyceride (TG) level, and CpG4 methylation ≥83%) vs terminal node 1 (CpG3 methylation <72%) (odds ratio 95% CI 0.20, 0.10‐0.40). Conclusions TXNIP methylation is associated with T2DM incidence in a Chinese population. Interaction between TXNIP methylation and environmental factors may influence T2DM risk and needs more investigation.