PMID- 33419631 OWN - NLM STAT- MEDLINE DCOM- 20220112 LR - 20220112 IS - 1873-460X (Electronic) IS - 1056-8727 (Linking) VI - 35 IP - 3 DP - 2021 Mar TI - Association of TCF7L2 gene polymorphisms, methylation, and gene-environment interaction with type 2 diabetes mellitus risk: A nested case-control study in the Rural Chinese Cohort Study. PG - 107829 LID - S1056-8727(20)30630-9 [pii] LID - 10.1016/j.jdiacomp.2020.107829 [doi] AB - BACKGROUND: To assess the associations of single-nucleotide polymorphisms (SNPs) and methylation of transcription factor 7-like 2 (TCF7L2) gene with type 2 diabetes mellitus (T2DM) risk and further explore the interactions among SNPs, methylation, and environmental factors involved in T2DM risk. METHODS: We conducted a nested case-control study with 290 pairs of T2DM cases and matched controls. We genotyped 3 SNPs of TCF7L2 in all included participants and tested 14 CpG loci of TCF7L2 in 76 pairs of cases and controls. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for T2DM risk according to SNPs and methylation of TCF7L2. Multifactor dimensionality reduction (MDR) analysis was used to explore the potential TCF7L2 gene-environment interactions in T2DM risk. RESULTS: We found no statistically significant association between the TCF7L2 polymorphisms and T2DM risk. We observed significant positive associations of methylation at CpG5 and CpG7_8 with T2DM risk. For each 1% increase in DNA methylation at CpG5 and CpG7_8, T2DM risk increased 12% (OR 1.12, 95% CI 1.01-1.25) and 32% (OR 1.32, 95% CI 1.07-1.63), respectively. Additionally, MDR analyses identified significant SNP-environment interactions among rs290487, alcohol drinking, and hypertension and methylation-environment interactions among CpG5, CpG7_8 and hypertension (P <0.05). CONCLUSIONS: TCF7L2 polymorphisms were not independently associated with T2DM risk. However, TCF7L2 methylation were positively associated with T2DM risk in rural Chinese adults. Interactions among TCF7L2 polymorphisms, TCF7L2 methylation and environmental factors also suggest a possible etiologic pattern for T2DM. CI - Copyright (c) 2020 Elsevier Inc. All rights reserved. FAU - Qie, Ranran AU - Qie R AD - Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China. FAU - Han, Minghui AU - Han M AD - Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China. FAU - Huang, Shengbing AU - Huang S AD - Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China. FAU - Li, Quanman AU - Li Q AD - Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China. FAU - Liu, Leilei AU - Liu L AD - Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China. FAU - Zhang, Dongdong AU - Zhang D AD - Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China. FAU - Cheng, Cheng AU - Cheng C AD - Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China. FAU - Zhao, Yang AU - Zhao Y AD - Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China. FAU - Liu, Dechen AU - Liu D AD - Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China. FAU - Qin, Pei AU - Qin P AD - Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China. FAU - Guo, Chunmei AU - Guo C AD - Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China. FAU - Zhou, Qionggui AU - Zhou Q AD - Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China. FAU - Tian, Gang AU - Tian G AD - Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China. FAU - Zhang, Yanyan AU - Zhang Y AD - Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China. FAU - Wu, Xiaoyan AU - Wu X AD - Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China. FAU - Wu, Yuying AU - Wu Y AD - Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China. FAU - Li, Yang AU - Li Y AD - Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China. FAU - Yang, Xingjin AU - Yang X AD - Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China. FAU - Zhao, Yang AU - Zhao Y AD - Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China. FAU - Feng, Yifei AU - Feng Y AD - Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China. FAU - Hu, Fulan AU - Hu F AD - Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China. FAU - Zhang, Ming AU - Zhang M AD - Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China. FAU - Hu, Dongsheng AU - Hu D AD - Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China. Electronic address: dongshenghu563@126.com. FAU - Lu, Jie AU - Lu J AD - Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China. Electronic address: hanyaa800@zzu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201231 PL - United States TA - J Diabetes Complications JT - Journal of diabetes and its complications JID - 9204583 RN - 0 (TCF7L2 protein, human) RN - 0 (Transcription Factor 7-Like 2 Protein) SB - IM MH - Adult MH - Case-Control Studies MH - China/epidemiology MH - Cohort Studies MH - *DNA Methylation MH - *Diabetes Mellitus, Type 2/epidemiology/genetics MH - Gene-Environment Interaction MH - *Genetic Predisposition to Disease MH - Humans MH - Hypertension MH - Polymorphism, Single Nucleotide MH - Rural Population MH - Transcription Factor 7-Like 2 Protein/*genetics OTO - NOTNLM OT - DNA methylation OT - Interaction OT - Polymorphism OT - TCF7L2 OT - Type 2 diabetes mellitus COIS- Declaration of competing interest The authors declare that they have no competing interests. EDAT- 2021/01/10 06:00 MHDA- 2022/01/13 06:00 CRDT- 2021/01/09 05:29 PHST- 2020/08/21 00:00 [received] PHST- 2020/11/08 00:00 [revised] PHST- 2020/12/01 00:00 [accepted] PHST- 2021/01/10 06:00 [pubmed] PHST- 2022/01/13 06:00 [medline] PHST- 2021/01/09 05:29 [entrez] AID - S1056-8727(20)30630-9 [pii] AID - 10.1016/j.jdiacomp.2020.107829 [doi] PST - ppublish SO - J Diabetes Complications. 2021 Mar;35(3):107829. doi: 10.1016/j.jdiacomp.2020.107829. Epub 2020 Dec 31.