CpG island shore methylation of ZFPM2 is identified in tetralogy of fallot samples

Pediatr Res. 2016 Jul;80(1):151-8. doi: 10.1038/pr.2016.42. Epub 2016 Mar 9.

Abstract

Background: ZFPM2 gene plays an important role in heart morphogenesis and development of coronary vessels from epicardium, however, little is known regarding its epigenetic regulation in the pathogenesis of tetralogy of fallot (TOF).

Methods: The methylation levels of ZFPM2 gene were measured by MassArray (Sequenom, San Diego, CA) and bisulfite sequencing polymerase chain reaction (PCR) (BSP). Real-time PCR was performed to analyze the mRNA levels for ZFPM2 gene in the myocardium of TOF.

Results: The methylation levels in the CpG island shore of ZFPM2 promoter were significantly higher in patients with TOF, with a median of 80.32% (interquartile range (IQR): 73.54-85.75%, N = 42), as compared to 59.63% in controls (IQR: 44.79-73.83%; P = 0.0186, N = 6). No significant difference was observed in the methylation status at the CpG island of ZFPM2 promoter. The ZFPM2 mRNA levels were significantly lower in patients with TOF compared to that in the controls (P < 0.05). The aberrant methylation values of ZFPM2 were negatively associated with significant changes in its mRNA level (r = -0.40, P = 0.008, N = 42).

Conclusion: Aberrant methylation status at the promoter CpG island shore of ZFPM2 gene may be associated with its gene transcription regulation in the TOF patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Child, Preschool
  • Cohort Studies
  • CpG Islands*
  • DNA Methylation*
  • DNA-Binding Proteins / genetics*
  • Epigenesis, Genetic
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Muscle Cells / cytology
  • Myocardium / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Pericardium / metabolism
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Sulfites / chemistry
  • Tetralogy of Fallot / genetics*
  • Transcription Factors / genetics*

Substances

  • DNA-Binding Proteins
  • RNA, Messenger
  • Sulfites
  • Transcription Factors
  • ZFPM2 protein, human
  • hydrogen sulfite