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TXNIP hypomethylation and its interaction with obesity and hypertriglyceridemia increase type 2 diabetes mellitus risk: A nested case-control study.
J Diabetes ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919985


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.


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.


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).


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.HIGHLIGHTS: This is the first prospective nested case-control study in rural Chinese people to estimate the association of the methylation level of the thioredoxin-interacting protein (TXNIP) gene and its interaction with type 2 diabetes mellitus (T2DM) risk. We found a significant negative association between the methylation level of TXNIP gene and T2DM incidence. Interaction among TXNIP gene hypomethylation, obesity, and hypertriglyceridemia increased the risk of T2DM.





Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Aspecto clínico: Etiologia Idioma: Inglês Assunto da revista: Endocrinologia Ano de publicação: 2020 Tipo de documento: Artigo País de afiliação: China