Preterm birth buccal cell epigenetic biomarkers to facilitate preventative medicine

Abstract

Preterm birth is the major cause of newborn and infant mortality affecting nearly one in every ten live births. The current study was designed to develop an epigenetic biomarker for susceptibility of preterm birth using buccal cells from the mother, father, and child (triads). An epigenome-wide association study (EWAS) was used to identify differential DNA methylation regions (DMRs) using a comparison of control term birth versus preterm birth triads. Epigenetic DMR associations with preterm birth were identified for both the mother and father that were distinct and suggest potential epigenetic contributions from both parents. The mother (165 DMRs) and female child (136 DMRs) at p < 1e−04 had the highest number of DMRs and were highly similar suggesting potential epigenetic inheritance of the epimutations. The male child had negligible DMR associations. The DMR associated genes for each group involve previously identified preterm birth associated genes. Observations identify a potential paternal germline contribution for preterm birth and identify the potential epigenetic inheritance of preterm birth susceptibility for the female child later in life. Although expanded clinical trials and preconception trials are required to optimize the potential epigenetic biomarkers, such epigenetic biomarkers may allow preventative medicine strategies to reduce the incidence of preterm birth.

Epigenome-wide association study of physical activity and physiological parameters in discordant monozygotic twins

“…The buccal cells were used as a marker cell for alterations in epigenetics for each individual. Similar analyses have been performed for disease specific comparisons, such as female susceptibility for arthritis [24][25][26][27][28] . The DNA was isolated from the buccal cells and used in a methylated DNA immunoprecipitation (MeDIP) protocol followed by next generation sequencing (MeDIP-Seq), as described in the Methods 24 .…”

“…Similar analyses have been performed for disease specific comparisons, such as female susceptibility for arthritis [24][25][26][27][28] . The DNA was isolated from the buccal cells and used in a methylated DNA immunoprecipitation (MeDIP) protocol followed by next generation sequencing (MeDIP-Seq), as described in the Methods 24 . The analysis and comparisons between the discordant twins for PA, walkability, and BMI were made for each sex (Fig.…”

“…A male and female separation of groups was made due to sex specific differences in epigenetics observed in previous studies 24,25 . Each individual's buccal cell epigenetic analysis was obtained such that optimal comparisons of parameters could be assessed.…”

“…This can be used as a marker cell for exposures and disease susceptibility. Recent studies have demonstrated buccal cells have epigenetic biomarkers for diseases such as arthritis or preterm birth 24,26 . Since ancestral and early life exposures can impact the majority of different cell types development and epigenetics, the current study used buccal cells as marker cells to identify physical activity exposure effects on epigenetics and make associations to metabolic parameters (e.g., BMI).…”

Immuno-epigenetic signature derived in saliva associates with the encephalopathy of prematurity and perinatal inflammatory disorders

“…DNAm is dynamic during fetal development, both in terms of the developing immune system (49) and brain (50)(51)(52) and may mediate the impact of maternal, fetal and postnatal exposures on brain development (53)(54)(55). In the context of preterm birth, only a limited number of studies have investigated DNAm changes (53,(56)(57)(58)(59)(60)(61)(62)(63)(64)(65) -of these, few examine DNAm in relation to neonatal neuroimaging metrics (59,62,63). Additionally, though some of these studies have examined DNAm in relation to postnatal health outcomes (53,65), no study to date has examined inflammation, DNAm, and neuroimaging concurrently in the neonatal period.…”