PMID- 35164795 OWN - NLM STAT- MEDLINE DCOM- 20220321 LR - 20220531 IS - 1479-5876 (Electronic) IS - 1479-5876 (Linking) VI - 20 IP - 1 DP - 2022 Feb 14 TI - Interaction between a diabetes-related methylation site (TXNIP cg19693031) and variant (GLUT1 rs841853) on fasting blood glucose levels among non-diabetics. PG - 87 LID - 10.1186/s12967-022-03269-y [doi] LID - 87 AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) is caused by a combination of environmental, genetic, and epigenetic factors including, fasting blood glucose (FBG), genetic variant rs841853, and cg19693031 methylation. We evaluated the interaction between rs841853 and cg19693031 on the FBG levels of non-diabetic Taiwanese adults. METHODS: We used Taiwan Biobank (TWB) data collected between 2008 and 2016. The TWB data source contains information on basic demographics, personal lifestyles, medical history, methylation, and genotype. The study participants included 1300 people with DNA methylation data. The association of cg19693031 methylation (stratified into quartiles) with rs841853 and FBG was determined using multiple linear regression analysis. The beta-coefficients (beta) and p-values were estimated. RESULTS: The mean +/- standard deviation (SD) of FBG in rs841853-CC individuals (92.07 +/- 7.78) did not differ significantly from that in the CA + AA individuals (91.62 +/- 7.14). However, the cg19693031 methylation levels were significantly different in the two groups (0.7716 +/- 0.05 in CC individuals and 0.7631 +/- 0.05 in CA + AA individuals (p = 0.002). The cg19693031 methylation levels according to quartiles were beta < 0.738592 (< Q1), 0.738592 /= 0.800918 (>/= Q3). FBG increased with decreasing cg19693031 methylation levels in a dose-response manner (p(trend) = 0.005). The beta-coefficient was - 0.0236 (p = 0.965) for Q2-Q3, 1.0317 (p = 0.058) for Q1-Q2, and 1.3336 (p = 0.019 for < Q1 compared to the reference quartile (>/= Q3). The genetic variant rs841853 was not significantly associated with FBG. However, its interaction with cg19693031 methylation was significant (p-value = 0.036). Based on stratification by rs841853 genotypes, only the CC group retained the inverse and dose-response association between FBG and cg19693031 methylation. The beta (p-value) was 0.8082 (0.255) for Q2-Q3, 1.6930 (0.022) for Q1-Q2, and 2.2190 (0.004) for < Q1 compared to the reference quartile (>/= Q3). The p(trend) was 0.002. CONCLUSION: Summarily, methylation at cg19693031 was inversely associated with fasting blood glucose in a dose-dependent manner. The inverse association was more prominent in rs841853-CC individuals, suggesting that rs841853 could modulate the association between cg19693031 methylation and FBG. Our results suggest that genetic variants may be involved in epigenetic mechanisms associated with FBG, a hallmark of diabetes. Therefore, integrating genetic and epigenetic data may provide more insight into the early-onset of diabetes. CI - (c) 2022. The Author(s). FAU - Tsai, Hao-Hung AU - Tsai HH AD - Institute of Medicine, Chung Shan Medical University, Taichung City, 40201, Taiwan. AD - School of Medicine, Chung Shan Medical University, Taichung, 40201, Taiwan. AD - School of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung, 40201, Taiwan. AD - Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung City, 40201, Taiwan. FAU - Shen, Chao-Yu AU - Shen CY AD - School of Medicine, Chung Shan Medical University, Taichung, 40201, Taiwan. AD - School of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung, 40201, Taiwan. AD - Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung City, 40201, Taiwan. FAU - Ho, Chien-Chang AU - Ho CC AD - Department of Physical Education, Fu Jen Catholic University, New Taipei, 24205, Taiwan. FAU - Hsu, Shu-Yi AU - Hsu SY AD - Department of Public Health and Institute of Public Health, Chung Shan Medical University, No. 110 Sect. 1 Jianguo N. Road, Taichung, 40201, Taiwan. FAU - Tantoh, Disline Manli AU - Tantoh DM AD - Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung City, 40201, Taiwan. AD - Department of Public Health and Institute of Public Health, Chung Shan Medical University, No. 110 Sect. 1 Jianguo N. Road, Taichung, 40201, Taiwan. FAU - Nfor, Oswald Ndi AU - Nfor ON AD - Department of Public Health and Institute of Public Health, Chung Shan Medical University, No. 110 Sect. 1 Jianguo N. Road, Taichung, 40201, Taiwan. FAU - Chiu, Shin-Lin AU - Chiu SL AD - Department of Ophthalmology, Changhua Christian Hospital, Changhua, Taiwan. AD - College of Nursing and Health Sciences, Da-Yeh University, Changhua, Taiwan. FAU - Chou, Ying-Hsiang AU - Chou YH AD - School of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung, 40201, Taiwan. hideka.chou@gmail.com. AD - Department of Radiation Oncology, Chung Shan Medical University Hospital, Taichung, 40201, Taiwan. hideka.chou@gmail.com. FAU - Liaw, Yung-Po AU - Liaw YP AUID- ORCID: 0000-0003-2046-4964 AD - Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung City, 40201, Taiwan. Liawyp@csmu.edu.tw. AD - Department of Public Health and Institute of Public Health, Chung Shan Medical University, No. 110 Sect. 1 Jianguo N. Road, Taichung, 40201, Taiwan. Liawyp@csmu.edu.tw. LA - eng GR - CSH-2021-D-006/Chung Shan Medical University Hospital/ GR - MOST 109-2121-M-040-002/Ministry of Science and Technology, Taiwan/ GR - MOST 110-2121-M-040-002/Ministry of Science and Technology, Taiwan/ GR - MOST 109-2811-M-040-500/Ministry of Science and Technology, Taiwan/ GR - MOST 110-2811-M-040-001/Ministry of Science and Technology, Taiwan/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220214 PL - England TA - J Transl Med JT - Journal of translational medicine JID - 101190741 RN - 0 (Blood Glucose) RN - 0 (Carrier Proteins) RN - 0 (Glucose Transporter Type 1) RN - 0 (SLC2A1 protein, human) RN - 0 (TXNIP protein, human) SB - IM MH - Adult MH - *Blood Glucose MH - Carrier Proteins/genetics MH - DNA Methylation/genetics MH - *Diabetes Mellitus, Type 2/genetics MH - Fasting MH - Glucose Transporter Type 1 MH - Humans PMC - PMC8842527 OTO - NOTNLM OT - Epigenetics OT - Fasting blood glucose OT - Genetic variants OT - Glucose transporter 1 OT - Interaction OT - Non-diabetics OT - Thioredoxin-interacting protein OT - cg19693031 OT - rs841853 COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest. EDAT- 2022/02/16 06:00 MHDA- 2022/03/22 06:00 PMCR- 2022/02/14 CRDT- 2022/02/15 05:31 PHST- 2021/10/29 00:00 [received] PHST- 2022/01/19 00:00 [accepted] PHST- 2022/02/15 05:31 [entrez] PHST- 2022/02/16 06:00 [pubmed] PHST- 2022/03/22 06:00 [medline] PHST- 2022/02/14 00:00 [pmc-release] AID - 10.1186/s12967-022-03269-y [pii] AID - 3269 [pii] AID - 10.1186/s12967-022-03269-y [doi] PST - epublish SO - J Transl Med. 2022 Feb 14;20(1):87. doi: 10.1186/s12967-022-03269-y.