PMID- 36316758
OWN - NLM
STAT- MEDLINE
DCOM- 20221102
LR  - 20221112
IS  - 1868-7083 (Electronic)
IS  - 1868-7075 (Print)
IS  - 1868-7075 (Linking)
VI  - 14
IP  - 1
DP  - 2022 Oct 31
TI  - Genome-wide DNA methylation analysis of extreme phenotypes in the identification 
      of novel epigenetic modifications in diabetic retinopathy.
PG  - 137
LID - 10.1186/s13148-022-01354-z [doi]
LID - 137
AB  - BACKGROUND: Aberrant epigenetic modifications such as DNA methylation may 
      contribute to the pathogenesis of DR. We aimed at elucidating the role of novel 
      DNA methylation modifications in diabetic retinopathy (DR) in patients with type 
      2 diabetes mellitus (T2DM) using an extreme phenotypic design. METHODS/RESULTS: 
      Two consecutive studies were conducted. A cross-sectional study using an extreme 
      phenotypic design was conducted to identify rare methylation modifications that 
      might contribute to DR pathogenesis. A 2-year longitudinal nested case-control 
      study was conducted to validate the results and assess whether these novel 
      methylation modifications could be used as biomarkers for predicting DR onset. A 
      large number of differentially methylated CpG sites were identified in the 
      cross-sectional study, and two (cg12869254 and cg04026387) corresponding to known 
      genes were replicated in the longitudinal study. Higher methylation of cg12869254 
      significantly correlated with macular RNFL thinning in the superior and nasal 
      subregions, and that of cg04026387 correlated with reduced deep capillary plexus 
      VD in the superior and inferior subregions after adjusting for covariates. 
      CONCLUSIONS: Cg12869254 and cg04026387 hypermethylation may complement the known 
      risk factors that contribute to the pathogenesis of DR and as novel biomarkers 
      for disease prediction.
CI  - (c) 2022. The Author(s).
FAU - Yang, Shaopeng
AU  - Yang S
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen 
      University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual 
      Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, 
      Guangzhou, China.
FAU - Guo, Xiao
AU  - Guo X
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen 
      University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual 
      Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, 
      Guangzhou, China.
FAU - Cheng, Weijing
AU  - Cheng W
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen 
      University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual 
      Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, 
      Guangzhou, China.
FAU - Seth, Ishith
AU  - Seth I
AD  - Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, 
      University of Melbourne, Level 7, 32 Gisborne Street, East Melbourne, VIC, 3002, 
      Australia.
FAU - Bulloch, Gabriella
AU  - Bulloch G
AD  - Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, 
      University of Melbourne, Level 7, 32 Gisborne Street, East Melbourne, VIC, 3002, 
      Australia.
FAU - Chen, Yifan
AU  - Chen Y
AD  - John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, 
      Oxford, UK.
FAU - Shang, Xianwen
AU  - Shang X
AD  - Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, 
      University of Melbourne, Level 7, 32 Gisborne Street, East Melbourne, VIC, 3002, 
      Australia.
FAU - Zhu, Zhuoting
AU  - Zhu Z
AD  - Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, 
      University of Melbourne, Level 7, 32 Gisborne Street, East Melbourne, VIC, 3002, 
      Australia.
FAU - Huang, Wenyong
AU  - Huang W
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen 
      University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual 
      Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, 
      Guangzhou, China.
FAU - Wang, Wei
AU  - Wang W
AUID- ORCID: 0000-0002-5273-3332
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen 
      University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual 
      Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, 
      Guangzhou, China. wangwei@gzzoc.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221031
PL  - Germany
TA  - Clin Epigenetics
JT  - Clinical epigenetics
JID - 101516977
RN  - 0 (Biomarkers)
SB  - IM
MH  - Humans
MH  - *Diabetic Retinopathy/genetics
MH  - DNA Methylation
MH  - *Diabetes Mellitus, Type 2/genetics
MH  - Case-Control Studies
MH  - Cross-Sectional Studies
MH  - Longitudinal Studies
MH  - Epigenesis, Genetic
MH  - Biomarkers
MH  - Phenotype
PMC - PMC9623976
OTO - NOTNLM
OT  - Biomarkers
OT  - DNA methylation
OT  - Diabetic retinopathy
OT  - Extreme phenotypes
OT  - Type 2 diabetes mellitus
COIS- The authors declare that they have no competing interests.
EDAT- 2022/11/02 06:00
MHDA- 2022/11/03 06:00
PMCR- 2022/10/31
CRDT- 2022/11/01 00:52
PHST- 2022/08/21 00:00 [received]
PHST- 2022/10/11 00:00 [accepted]
PHST- 2022/11/01 00:52 [entrez]
PHST- 2022/11/02 06:00 [pubmed]
PHST- 2022/11/03 06:00 [medline]
PHST- 2022/10/31 00:00 [pmc-release]
AID - 10.1186/s13148-022-01354-z [pii]
AID - 1354 [pii]
AID - 10.1186/s13148-022-01354-z [doi]
PST - epublish
SO  - Clin Epigenetics. 2022 Oct 31;14(1):137. doi: 10.1186/s13148-022-01354-z.