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

Catherine M Bulka, Olaf Dammann, Hudson P Santos Jr, Deborah K VanderVeen, Lisa Smeester, Raina Fichorova, T Michael O’Shea, Rebecca C Fry

Invest Ophthalmol Vis Sci. 2019 Jul 1;60(8):2888-2894.

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We previously identified inflammatory proteins expressed early in life and associated with risk of ROP in EP while angiogenic and neurotrophic growth factors are associated with lower risk of ROP. In this paper, we test hypothesis that placental CpG methylation levels of 12 inflammation-, angiogenic-, and neurotrophic-associated genes predict prethreshold ROP in EP newborns. We used placental CpG methylation data from 395 newborns from ELGAN study.

Placental DNA methylation of 16 CpG sites representing 8 genes associated with prethreshold ROP. Specifically, CpG methylation in 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. Conversely, CpG methylation within TNF receptor superfamily member 1A (TNFRSF1A) and in BDNF and ANGPT1 genes were associated with increased risk of ROP. CpG methylation may be a useful marker for improving ROP prediction.