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Infant peripheral blood repetitive element hypomethylation associated with antiretroviral therapy in utero.

ABSTRACT: The use of combination antiretroviral therapy (cART) to prevent HIV mother-to-child transmission during pregnancy and delivery is generally considered safe. However, vigilant assessment of potential risks of these agents remains warranted. Epigenetic changes including DNA methylation are considered potential mechanisms linking the in utero environment with long-term health outcomes. Few studies have examined the epigenetic effects of prenatal exposure to pharmaceutical agents, including antiretroviral therapies, on children. In this study, we examined the methylation status of the LINE-1 and ALU-Yb8 repetitive elements as markers of global DNA methylation alteration in peripheral blood mononuclear cells obtained from newborns participating in the Pediatric HIV/AIDS Cohort Study SMARTT cohort of HIV-exposed, cART-exposed uninfected infants compared to a historical cohort of HIV-exposed, antiretroviral-unexposed infants from the Women and Infants Transmission Study Cohort. In linear regression models controlling for potential confounders, we found the adjusted mean difference of AluYb8 methylation of the cART-exposed compared to the -unexposed was -0.568 (95% CI: -1.023, -0.149) and for LINE-1 methylation was -1.359 (95% CI: -1.860, -0.857). Among those exposed to cART, subjects treated with atazanavir (ATV), compared to those on other treatments, had less AluYb8 methylation (-0.524, 95% CI: -0.025, -1.024). Overall, these results suggest a small but statistically significant reduction in the methylation of these repetitive elements in an HIV-exposed, cART-exposed cohort compared to an HIV-exposed, cART-unexposed historic cohort. The potential long-term implications of these differences are worthy of further examination.

SUBMITTER: Marsit CJ

PROVIDER: S-EPMC4622750 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Infant peripheral blood repetitive element hypomethylation associated with antiretroviral therapy in utero.

Marsit Carmen J CJ Brummel Sean S SS Kacanek Deborah D Seage George R GR Spector Stephen A SA Armstrong David A DA Lester Barry M BM Rich Kenneth K

Epigenetics 20150101 8

The use of combination antiretroviral therapy (cART) to prevent HIV mother-to-child transmission during pregnancy and delivery is generally considered safe. However, vigilant assessment of potential risks of these agents remains warranted. Epigenetic changes including DNA methylation are considered potential mechanisms linking the in utero environment with long-term health outcomes. Few studies have examined the epigenetic effects of prenatal exposure to pharmaceutical agents, including antiretr ...[more]

PMID: 26067216

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Project description:BackgroundFetal programming describes the theory linking environmental conditions during embryonic and fetal development with risk of diseases later in life. Environmental insults in utero may lead to changes in epigenetic mechanisms potentially affecting fetal development.ObjectivesWe examined associations between in utero exposures, infant growth, and methylation of repetitive elements and gene-associated DNA in human term placenta tissue samples.MethodsPlacental tissues and associated demographic and clinical data were obtained from subjects delivering at Women and Infants Hospital in Providence, Rhode Island (USA). Methylation levels of long interspersed nuclear element-1 (LINE-1) and the Alu element AluYb8 were determined in 380 placental samples from term deliveries using bisulfite pyrosequencing. Genomewide DNA methylation profiles were obtained in a subset of 184 samples using the Illumina Infinium HumanMethylation27 BeadArray. Multiple linear regression, model-based clustering methods, and gene set enrichment analysis examined the association between birth weight percentile, demographic variables, and repetitive element methylation and gene-associated CpG locus methylation.ResultsLINE-1 and AluYb8 methylation levels were found to be significantly positively associated with birth weight percentile (p = 0.01 and p < 0.0001, respectively) and were found to differ significantly among infants exposed to tobacco smoke and alcohol. Increased placental AluYb8 methylation was positively associated with average methylation among CpG loci found in polycomb group target genes; developmentally related transcription factor binding sites were overrepresented for differentially methylated loci associated with both elements.ConclusionsOur results suggest that repetitive element methylation markers, most notably AluYb8 methylation, may be susceptible to epigenetic alterations resulting from the intrauterine environment and play a critical role in mediating placenta function, and may ultimately inform on the developmental basis of health and disease.

Dataset Information

Infant peripheral blood repetitive element hypomethylation associated with antiretroviral therapy in utero.

Publications

Infant peripheral blood repetitive element hypomethylation associated with antiretroviral therapy in utero.

Similar Datasets

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