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Invest Ophthalmol Vis Sci. 2019 Jul 1;60(8):2888-2894. doi: 10.1167/iovs.18-26466.

Placental CpG Methylation of Inflammation, Angiogenic, and Neurotrophic Genes and Retinopathy of Prematurity.

Author information

1
Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, United States.
2
Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, Massachusetts, United States.
3
Perinatal Neuroepidemiology Unit, Department of Gynecology and Obstetrics, Hannover Medical School, Hannover, Germany.
4
School of Nursing, University of North Carolina, Chapel Hill, North Carolina, United States.
5
Department of Ophthalmology, Boston Children's Hospital, Boston, Massachusetts, United States.
6
Institute for Environmental Health Solutions, Gilling School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, United States.
7
Department of Obstetrics, Gynecology and Reproductive Biology, Brigham And Women's Hospital, Boston, Massachusetts, United States.
8
Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina, United States.
9
Curriculum in Toxicology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States.

Abstract

Purpose:

Extremely preterm infants are at increased risk for retinopathy of prematurity (ROP). We previously identified several inflammatory proteins that were expressed early in life and are associated with an increased risk of ROP and several angiogenic and neurotrophic growth factors in the neonatal systemic circulation that are associated with a lower risk of ROP. In this paper, we report the results of a set of analyses designed to test the hypothesis that placental CpG methylation levels of 12 inflammation-, angiogenic-, and neurotrophic-associated genes predict the occurrence of prethreshold ROP in extremely preterm newborns.

Methods:

We used placental CpG methylation data from 395 newborns from the Extremely Low Gestational Age Newborns study.

Results:

Multivariable regression models revealed that placental DNA methylation of 16 CpG sites representing 8 genes were associated with prethreshold ROP. Specifically, CpG methylation in the serum amyloid A SAA1 and SAA2, brain-derived neurotrophic factor (BDNF), myeloperoxidase (MPO), C-reactive protein (CRP), angiopoietin 1 (ANGPT1), and tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) genes was associated with a lower risk of prethreshold ROP. Conversely, CpG methylation at three probes within tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) and in two alternative probes within the BDNF and ANGPT1 genes was associated with an increased risk of ROP.

Conclusions:

CpG methylation may be a useful marker for improving ROP prediction, opening the opportunity for early intervention to lessen disease severity.

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