PMID- 37461060
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230720
IS  - 1758-5996 (Print)
IS  - 1758-5996 (Electronic)
IS  - 1758-5996 (Linking)
VI  - 15
IP  - 1
DP  - 2023 Jul 17
TI  - Identification of key DNA methylation changes on fasting plasma glucose: a 
      genome-wide DNA methylation analysis in Chinese monozygotic twins.
PG  - 159
LID - 10.1186/s13098-023-01136-4 [doi]
LID - 159
AB  - BACKGROUND: Elevated fasting plasma glucose (FPG) levels can increase morbidity 
      and mortality even when it is below the diagnostic threshold of type 2 diabetes 
      mellitus (T2DM). We conducted a genome-wide DNA methylation analysis to detect 
      DNA methylation (DNAm) variants potentially related to FPG in Chinese monozygotic 
      twins. METHODS: Genome-wide DNA methylation profiling in whole blood of twins was 
      performed using Reduced Representation Bisulfite Sequencing (RRBS), yielding 
      551,447 raw CpGs. Association between DNAm of single CpG and FPG was tested using 
      a generalized estimation equation. Differentially methylated regions (DMRs) were 
      identified using comb-P approach. ICE FALCON method was utilized to perform the 
      causal inference. Candidate CpGs were quantified and validated using Sequenom 
      MassARRAY platform in a community population. Weighted gene co-expression network 
      analysis (WGCNA) was conducted using gene expression data from twins. RESULTS: 
      The mean age of 52 twin pairs was 52 years (SD: 7). The relationship between DNAm 
      of 142 CpGs and FPG reached the genome-wide significance level. Thirty-two DMRs 
      within 24 genes were identified, including TLCD1, MRPS31P5, CASZ1, and CXADRP3. 
      The causal relationship of top CpGs mapped to TLCD1, MZF1, PTPRN2, SLC6A18, 
      ASTN2, IQCA1, GRIN1, and PDE2A genes with FPG were further identified using ICE 
      FALCON method. Pathways potentially related to FPG were also identified, such as 
      phospholipid-hydroperoxide glutathione peroxidase activity and mitogen-activated 
      protein kinase p38 binding. Three CpGs mapped to SLC6A18 gene were validated in a 
      community population, with a hypermethylated direction in diabetic patients. The 
      expression levels of 18 genes (including SLC6A18 and TLCD1) were positively 
      correlated with FPG levels. CONCLUSIONS: We detect many DNAm variants that may be 
      associated with FPG in whole blood, particularly the loci within SLC6A18 gene. 
      Our findings provide important reference for the epigenetic regulation of 
      elevated FPG levels and diabetes.
CI  - (c) 2023. The Author(s).
FAU - Wang, Weijing
AU  - Wang W
AUID- ORCID: 0000-0001-7747-7649
AD  - Department of Epidemiology and Health Statistics, School of Public Health, 
      Qingdao University, No. 308 Ningxia Road, Qingdao, 266071, Shandong Province, 
      China. wangwj793@126.com.
FAU - Yao, Wenqin
AU  - Yao W
AD  - Department of Epidemiology and Health Statistics, School of Public Health, 
      Qingdao University, No. 308 Ningxia Road, Qingdao, 266071, Shandong Province, 
      China.
AD  - Shandong Province Center for Disease Control and Prevention, Shandong, China.
FAU - Tan, Qihua
AU  - Tan Q
AD  - Epidemiology and Biostatistics, Department of Public Health, University of 
      Southern Denmark, Odense, Denmark.
FAU - Li, Shuxia
AU  - Li S
AD  - Epidemiology and Biostatistics, Department of Public Health, University of 
      Southern Denmark, Odense, Denmark.
FAU - Duan, Haiping
AU  - Duan H
AD  - Qingdao Municipal Center for Disease Control and Prevention/Qingdao Institute of 
      Preventive Medicine, Qingdao, Shandong, China.
FAU - Tian, Xiaocao
AU  - Tian X
AD  - Qingdao Municipal Center for Disease Control and Prevention/Qingdao Institute of 
      Preventive Medicine, Qingdao, Shandong, China.
FAU - Xu, Chunsheng
AU  - Xu C
AD  - Qingdao Municipal Center for Disease Control and Prevention/Qingdao Institute of 
      Preventive Medicine, Qingdao, Shandong, China.
FAU - Zhang, Dongfeng
AU  - Zhang D
AD  - Department of Epidemiology and Health Statistics, School of Public Health, 
      Qingdao University, No. 308 Ningxia Road, Qingdao, 266071, Shandong Province, 
      China.
LA  - eng
GR  - ZR2020QH304/Natural Science Foundation of Shandong Province/
GR  - 2020M682129/China Postdoctoral Science Foundation/
GR  - 31741063/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20230717
PL  - England
TA  - Diabetol Metab Syndr
JT  - Diabetology & metabolic syndrome
JID - 101488958
PMC - PMC10351111
OTO - NOTNLM
OT  - Causality
OT  - DNA methylation
OT  - Fasting plasma glucose
OT  - Monozygotic twins
COIS- The authors declare that they have no competing interests.
EDAT- 2023/07/18 01:09
MHDA- 2023/07/18 01:10
PMCR- 2023/07/17
CRDT- 2023/07/17 23:48
PHST- 2023/03/29 00:00 [received]
PHST- 2023/07/09 00:00 [accepted]
PHST- 2023/07/18 01:10 [medline]
PHST- 2023/07/18 01:09 [pubmed]
PHST- 2023/07/17 23:48 [entrez]
PHST- 2023/07/17 00:00 [pmc-release]
AID - 10.1186/s13098-023-01136-4 [pii]
AID - 1136 [pii]
AID - 10.1186/s13098-023-01136-4 [doi]
PST - epublish
SO  - Diabetol Metab Syndr. 2023 Jul 17;15(1):159. doi: 10.1186/s13098-023-01136-4.