Placental epigenetics for evaluation of fetal congenital heart defects

Ventricular septal defect (VSD)

Uppala Radhakrishna, Samet Albayrak, Rita Zafra, Alosh Baraa, Sangeetha Vishweswaraiah, Avinash M. Veerappa, Deepthi Mahishi, Nazia Saiyed, Nitish K. Mishra, Chittibabu Guda, Rouba Ali-Fehmi, Ray O. Bahado-Singh

Research output: Contribution to journalArticle

Abstract

Ventricular Septal Defect (VSD), the most common congenital heart defect, is characterized by a hole in the septum between the right and left ventricles. The pathogenesis of VSD is unknown in most clinical cases. There is a paucity of data relevant to epigenetic changes in VSD. The placenta is a fetal tissue crucial in cardiac development and a potentially useful surrogate for evaluating the development of heart tissue. To understand epigenetic mechanisms that may play a role in the development of VSD, genome-wide DNA methylation assay on placentas of 8 term subjects with isolated VSD and no known or suspected genetic syndromes and 10 unaffected controls was performed using the Illumina HumanMethyla-tion450 BeadChip assay. We identified a total of 80 highly accurate potential CpGs in 80 genes for detection of VSD; area under the receiver operating characteristic curve (AUC ROC) 1.0 with significant 95% CI (FDR) p-values < 0.05 for each individual locus. The biological processes and functions for many of these differentially methylated genes are previously known to be associated with heart development or disease, including cardiac ventricle development (HEY2, ISL1), heart looping (SRF), cardiac muscle cell differentiation (ACTC1, HEY2), cardiac septum development (ISL1), heart morphogenesis (SRF, HEY2, ISL1, HEYL), Notch signaling pathway (HEY2, HEYL), cardiac chamber development (ISL1), and cardiac muscle tissue development (ACTC1, ISL1). In addition, we identified 8 microRNAs that have the potential to be biomarkers for the detection of VSD including: miR-191, miR-548F1, miR-148A, miR-423, miR-92B, miR-611, miR-2110, and miR-548H4. To our knowledge this is the first report in which placental analysis has been used for determining the pathogenesis of and predicting VSD.

Original languageEnglish (US)
Article numbere0200229
JournalPloS one
Volume14
Issue number3
DOIs
StatePublished - Mar 1 2019

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Fetal Heart
Congenital Heart Defects
Ventricular Heart Septal Defects
Epigenomics
epigenetics
heart
Defects
placenta
Heart Ventricles
pathogenesis
Genes
ROC Curve
Tissue
Placenta
heart diseases
assays
DNA methylation
myocardium
Heart Septum
microRNA

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Radhakrishna, U., Albayrak, S., Zafra, R., Baraa, A., Vishweswaraiah, S., Veerappa, A. M., ... Bahado-Singh, R. O. (2019). Placental epigenetics for evaluation of fetal congenital heart defects: Ventricular septal defect (VSD). PloS one, 14(3), [e0200229]. https://doi.org/10.1371/journal.pone.0200229

Placental epigenetics for evaluation of fetal congenital heart defects : Ventricular septal defect (VSD). / Radhakrishna, Uppala; Albayrak, Samet; Zafra, Rita; Baraa, Alosh; Vishweswaraiah, Sangeetha; Veerappa, Avinash M.; Mahishi, Deepthi; Saiyed, Nazia; Mishra, Nitish K.; Guda, Chittibabu; Ali-Fehmi, Rouba; Bahado-Singh, Ray O.

In: PloS one, Vol. 14, No. 3, e0200229, 01.03.2019.

Research output: Contribution to journalArticle

Radhakrishna, U, Albayrak, S, Zafra, R, Baraa, A, Vishweswaraiah, S, Veerappa, AM, Mahishi, D, Saiyed, N, Mishra, NK, Guda, C, Ali-Fehmi, R & Bahado-Singh, RO 2019, 'Placental epigenetics for evaluation of fetal congenital heart defects: Ventricular septal defect (VSD)', PloS one, vol. 14, no. 3, e0200229. https://doi.org/10.1371/journal.pone.0200229
Radhakrishna U, Albayrak S, Zafra R, Baraa A, Vishweswaraiah S, Veerappa AM et al. Placental epigenetics for evaluation of fetal congenital heart defects: Ventricular septal defect (VSD). PloS one. 2019 Mar 1;14(3). e0200229. https://doi.org/10.1371/journal.pone.0200229
Radhakrishna, Uppala ; Albayrak, Samet ; Zafra, Rita ; Baraa, Alosh ; Vishweswaraiah, Sangeetha ; Veerappa, Avinash M. ; Mahishi, Deepthi ; Saiyed, Nazia ; Mishra, Nitish K. ; Guda, Chittibabu ; Ali-Fehmi, Rouba ; Bahado-Singh, Ray O. / Placental epigenetics for evaluation of fetal congenital heart defects : Ventricular septal defect (VSD). In: PloS one. 2019 ; Vol. 14, No. 3.
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abstract = "Ventricular Septal Defect (VSD), the most common congenital heart defect, is characterized by a hole in the septum between the right and left ventricles. The pathogenesis of VSD is unknown in most clinical cases. There is a paucity of data relevant to epigenetic changes in VSD. The placenta is a fetal tissue crucial in cardiac development and a potentially useful surrogate for evaluating the development of heart tissue. To understand epigenetic mechanisms that may play a role in the development of VSD, genome-wide DNA methylation assay on placentas of 8 term subjects with isolated VSD and no known or suspected genetic syndromes and 10 unaffected controls was performed using the Illumina HumanMethyla-tion450 BeadChip assay. We identified a total of 80 highly accurate potential CpGs in 80 genes for detection of VSD; area under the receiver operating characteristic curve (AUC ROC) 1.0 with significant 95{\%} CI (FDR) p-values < 0.05 for each individual locus. The biological processes and functions for many of these differentially methylated genes are previously known to be associated with heart development or disease, including cardiac ventricle development (HEY2, ISL1), heart looping (SRF), cardiac muscle cell differentiation (ACTC1, HEY2), cardiac septum development (ISL1), heart morphogenesis (SRF, HEY2, ISL1, HEYL), Notch signaling pathway (HEY2, HEYL), cardiac chamber development (ISL1), and cardiac muscle tissue development (ACTC1, ISL1). In addition, we identified 8 microRNAs that have the potential to be biomarkers for the detection of VSD including: miR-191, miR-548F1, miR-148A, miR-423, miR-92B, miR-611, miR-2110, and miR-548H4. To our knowledge this is the first report in which placental analysis has been used for determining the pathogenesis of and predicting VSD.",
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AU - Vishweswaraiah, Sangeetha

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AU - Mahishi, Deepthi

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