TXNIP hypomethylation and its interaction with obesity and hypertriglyceridemia increase type 2 diabetes mellitus risk: A nested case-control study
TXNIP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
Dongdong Zhang
Center for Community Health Management, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, China
School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, China
Search for more papers by this authorCheng Cheng
Center for Community Health Management, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, China
School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, China
Search for more papers by this authorMeng Cao
Department of Environmental Health, Jinan Center for Disease Control and Prevention, Jinan, Shandong, China
Search for more papers by this authorTieqiang Wang
Key Lab of Epidemiology, Department of Infectious Disease Control and Prevention, Shenzhen Guangming District Center for Disease Control and Prevention, Shenzhen, Guangdong, China
Search for more papers by this authorXiaoliang Chen
Key Lab of Epidemiology, Department of Infectious Disease Control and Prevention, Shenzhen Guangming District Center for Disease Control and Prevention, Shenzhen, Guangdong, China
Search for more papers by this authorYang Zhao
Center for Community Health Management, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, China
School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, China
Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China
Search for more papers by this authorBingyuan Wang
Center for Community Health Management, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, China
School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, China
Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China
Search for more papers by this authorYongcheng Ren
Center for Community Health Management, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, China
School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, China
Key Lab of Epidemiology, Department of Infectious Disease Control and Prevention, Shenzhen Guangming District Center for Disease Control and Prevention, Shenzhen, Guangdong, China
Search for more papers by this authorDechen Liu
Center for Community Health Management, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, China
School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, China
Key Lab of Epidemiology, Department of Infectious Disease Control and Prevention, Shenzhen Guangming District Center for Disease Control and Prevention, Shenzhen, Guangdong, China
Search for more papers by this authorLeilei Liu
Center for Community Health Management, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, China
School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, China
Search for more papers by this authorXu Chen
Center for Community Health Management, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, China
Search for more papers by this authorFeiyan Liu
Center for Community Health Management, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, China
Search for more papers by this authorQionggui Zhou
Center for Community Health Management, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, China
Search for more papers by this authorGang Tian
Key Lab of Epidemiology, Department of Infectious Disease Control and Prevention, Shenzhen Guangming District Center for Disease Control and Prevention, Shenzhen, Guangdong, China
Search for more papers by this authorQuanman Li
Key Lab of Epidemiology, Department of Infectious Disease Control and Prevention, Shenzhen Guangming District Center for Disease Control and Prevention, Shenzhen, Guangdong, China
Search for more papers by this authorChunmei Guo
Key Lab of Epidemiology, Department of Infectious Disease Control and Prevention, Shenzhen Guangming District Center for Disease Control and Prevention, Shenzhen, Guangdong, China
Search for more papers by this authorHonghui Li
Center for Community Health Management, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, China
Search for more papers by this authorJian Wang
Center for Community Health Management, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, China
Search for more papers by this authorRuirong Cheng
Center for Community Health Management, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, China
Search for more papers by this authorDongsheng Hu
Center for Community Health Management, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, China
School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, China
Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China
Search for more papers by this authorCorresponding Author
Ming Zhang
Center for Community Health Management, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, China
School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, China
Correspondence
Ming Zhang, School of Public Health, Shenzhen University Health Sciences Center, No. 3688 Nanhai Avenue, Nanshan District, Shenzhen, Guangdong 518060, China.
Email: [email protected]
Search for more papers by this authorDongdong Zhang
Center for Community Health Management, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, China
School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, China
Search for more papers by this authorCheng Cheng
Center for Community Health Management, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, China
School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, China
Search for more papers by this authorMeng Cao
Department of Environmental Health, Jinan Center for Disease Control and Prevention, Jinan, Shandong, China
Search for more papers by this authorTieqiang Wang
Key Lab of Epidemiology, Department of Infectious Disease Control and Prevention, Shenzhen Guangming District Center for Disease Control and Prevention, Shenzhen, Guangdong, China
Search for more papers by this authorXiaoliang Chen
Key Lab of Epidemiology, Department of Infectious Disease Control and Prevention, Shenzhen Guangming District Center for Disease Control and Prevention, Shenzhen, Guangdong, China
Search for more papers by this authorYang Zhao
Center for Community Health Management, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, China
School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, China
Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China
Search for more papers by this authorBingyuan Wang
Center for Community Health Management, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, China
School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, China
Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China
Search for more papers by this authorYongcheng Ren
Center for Community Health Management, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, China
School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, China
Key Lab of Epidemiology, Department of Infectious Disease Control and Prevention, Shenzhen Guangming District Center for Disease Control and Prevention, Shenzhen, Guangdong, China
Search for more papers by this authorDechen Liu
Center for Community Health Management, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, China
School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, China
Key Lab of Epidemiology, Department of Infectious Disease Control and Prevention, Shenzhen Guangming District Center for Disease Control and Prevention, Shenzhen, Guangdong, China
Search for more papers by this authorLeilei Liu
Center for Community Health Management, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, China
School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, China
Search for more papers by this authorXu Chen
Center for Community Health Management, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, China
Search for more papers by this authorFeiyan Liu
Center for Community Health Management, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, China
Search for more papers by this authorQionggui Zhou
Center for Community Health Management, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, China
Search for more papers by this authorGang Tian
Key Lab of Epidemiology, Department of Infectious Disease Control and Prevention, Shenzhen Guangming District Center for Disease Control and Prevention, Shenzhen, Guangdong, China
Search for more papers by this authorQuanman Li
Key Lab of Epidemiology, Department of Infectious Disease Control and Prevention, Shenzhen Guangming District Center for Disease Control and Prevention, Shenzhen, Guangdong, China
Search for more papers by this authorChunmei Guo
Key Lab of Epidemiology, Department of Infectious Disease Control and Prevention, Shenzhen Guangming District Center for Disease Control and Prevention, Shenzhen, Guangdong, China
Search for more papers by this authorHonghui Li
Center for Community Health Management, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, China
Search for more papers by this authorJian Wang
Center for Community Health Management, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, China
Search for more papers by this authorRuirong Cheng
Center for Community Health Management, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, China
Search for more papers by this authorDongsheng Hu
Center for Community Health Management, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, China
School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, China
Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China
Search for more papers by this authorCorresponding Author
Ming Zhang
Center for Community Health Management, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, China
School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, China
Correspondence
Ming Zhang, School of Public Health, Shenzhen University Health Sciences Center, No. 3688 Nanhai Avenue, Nanshan District, Shenzhen, Guangdong 518060, China.
Email: [email protected]
Search for more papers by this authorAbstract
enBackground
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.
摘要
zh背景
本研究旨在分析TXNIP基因甲基化及其与环境因素的交互作用与2型糖尿病(type 2 diabetes mellitus, T2DM)发病风险之间的关联。
方法
本研究采用病例对照研究设计, 在中国农村队列研究中按照年龄、性别、婚姻状况、种族和居住地五等条件进行1:1匹配, 纳入病例、对照各286人。采用条件logistic回归模型, 分析TXNIP基因甲基化与T2DM之间的关联; 采用多因素降维法(multifactor dimensionality reduction,MDR)和分类回归树(classification and regression tree, CART)评价TXNIP甲基化与环境风险因素之间的交互作用。
结果
T2DM组TXNIP基因的5个CpG位点甲基化水平均显著低于对照组(P<0.001)。随着甲基化水平的增加, T2DM风险显著降低(OR [95%CI]:CpG1, 0.80 [0.69-0.94]; CpG2, 0.80 [0.69-0.93]; CpG3, 0.70 [0.56-0.88]; CpG4, 0.78 [0.66-0.92]; CpG5, 0.76 [0.60-0.97])。此外, CART和MDR结果显示, TXNIP甲基化、肥胖和高甘油三酯血症之间存在交互作用。Logistic回归分析显示, 与终末节点1亚组人群(CpG3甲基化<72%)相比, 终末节点5亚组人群(CpG3甲基化≥72%、非肥胖、甘油三酯(TG)水平正常, 且CpG4甲基化≥83%)发生T2DM的风险较低(OR=0.20, 95%CI:0.10~0.40)。
结论
在中国人群中, TXNIP基因甲基化水平与T2DM的发生风险有关。TXNIP甲基化与环境因素的交互作用可能影响T2DM风险, 但还需要进一步研究。
CONFLICT OF INTEREST
The authors declare no conflict of interests.
Supporting Information
| Filename | Description |
|---|---|
| jdb13021-sup-0001-Supinfo.docxWord 2007 document , 1.3 MB | Appendix S1. Supporting Information. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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