Newborn blood DNA epigenetic variations and signaling pathway genes associated with Tetralogy of Fallot (TOF)

Uppala Radhakrishna, Sangeetha Vishweswaraiah, Avinash M. Veerappa, Rita Zafra, Samet Albayrak, Prajna H. Sitharam, Nazia M. Saiyed, Nitish K. Mishra, Chittibabu Guda, Ray Bahado-Singh

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Tetralogy of Fallot (TOF) is the most common Critical Congenital Heart Defect (CCHD). The etiology of TOF is unknown in most cases. Preliminary data from our group and others suggest that epigenetic changes may play an important role in CHD. Epidemiologically, a significant percentage of CHD including TOF fail to be diagnosed in the prenatal and early newborn period which can negatively affect health outcomes. We performed genome-wide methylation assay in newborn blood in 24 non-syndromic TOF cases and 24 unaffected matched controls using Illumina Infinium HumanMethylation450 BeadChips. We identified 64 significantly differentially methylated CpG sites in TOF cases, of which 25 CpG sites had high predictive accuracy for TOF, based on the area under the receiver operating characteristics curve (AUC ROC) 0.90). The CpG methylation difference between TOF and controls was 10% in 51 CpG targets suggesting biological significance. Gene ontology analysis identified significant biological processes and functions related to these differentially methylated genes, including: CHD development, cardiomyopathy, diabetes, immunological, inflammation and other plausible pathways in CHD development. Multiple genes known or plausibly linked to heart development and post-natal heart disease were found to be differentially methylated in the blood DNA of newborns with TOF including: ABCB1, PPP2R5C, TLR1, SELL, SCN3A, CREM, RUNX and LHX9. We generated novel and highly accurate putative molecular markers for TOF detection using leucocyte DNA and thus provided information on pathogenesis of TOF.

Original languageEnglish (US)
Article numbere0203893
JournalPloS one
Volume13
Issue number9
DOIs
StatePublished - Sep 2018

Fingerprint

Tetralogy of Fallot
Epigenomics
epigenetics
neonates
Blood
Genes
methylation
Methylation
DNA
blood
heart
genes
cardiomyopathy
heart diseases
diabetes
etiology
leukocytes
pathogenesis
Medical problems
inflammation

ASJC Scopus subject areas

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

Cite this

Radhakrishna, U., Vishweswaraiah, S., Veerappa, A. M., Zafra, R., Albayrak, S., Sitharam, P. H., ... Bahado-Singh, R. (2018). Newborn blood DNA epigenetic variations and signaling pathway genes associated with Tetralogy of Fallot (TOF). PloS one, 13(9), [e0203893]. https://doi.org/10.1371/journal.pone.0203893

Newborn blood DNA epigenetic variations and signaling pathway genes associated with Tetralogy of Fallot (TOF). / Radhakrishna, Uppala; Vishweswaraiah, Sangeetha; Veerappa, Avinash M.; Zafra, Rita; Albayrak, Samet; Sitharam, Prajna H.; Saiyed, Nazia M.; Mishra, Nitish K.; Guda, Chittibabu; Bahado-Singh, Ray.

In: PloS one, Vol. 13, No. 9, e0203893, 09.2018.

Research output: Contribution to journalArticle

Radhakrishna, U, Vishweswaraiah, S, Veerappa, AM, Zafra, R, Albayrak, S, Sitharam, PH, Saiyed, NM, Mishra, NK, Guda, C & Bahado-Singh, R 2018, 'Newborn blood DNA epigenetic variations and signaling pathway genes associated with Tetralogy of Fallot (TOF)', PloS one, vol. 13, no. 9, e0203893. https://doi.org/10.1371/journal.pone.0203893
Radhakrishna U, Vishweswaraiah S, Veerappa AM, Zafra R, Albayrak S, Sitharam PH et al. Newborn blood DNA epigenetic variations and signaling pathway genes associated with Tetralogy of Fallot (TOF). PloS one. 2018 Sep;13(9). e0203893. https://doi.org/10.1371/journal.pone.0203893
Radhakrishna, Uppala ; Vishweswaraiah, Sangeetha ; Veerappa, Avinash M. ; Zafra, Rita ; Albayrak, Samet ; Sitharam, Prajna H. ; Saiyed, Nazia M. ; Mishra, Nitish K. ; Guda, Chittibabu ; Bahado-Singh, Ray. / Newborn blood DNA epigenetic variations and signaling pathway genes associated with Tetralogy of Fallot (TOF). In: PloS one. 2018 ; Vol. 13, No. 9.
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