title: HIRAGene is Lower Expressed in the Myocardium of Patients with Tetralogy of Fallot.
abstract: BACKGROUND
  The most typical cardiac abnormality is conotruncal defects (CTDs) in patients with 22q11 deletion syndrome (22q11DS). HIRA (histone cell cycle regulator) gene, as one of the candidate genes located at the critical region of 22q11DS, was reported as possibly relevant to CTD in animal models. This study aimed to analyze the level of expression of the HIRA gene in tetralogy of Fallot (TOF) patients and the potential DNA sequence variations in the promoter region.
  
  
  METHODS
  The messenger RNA (mRNA) expression was examined with quantitative real-time polymerase chain reaction in 39 myocardial tissues of the right ventricular outflow tract (RVOT) from TOF patients and 4 myocardial tissues of RVOT from noncardiac death children. The protein expression was detected using immunohistochemistry in 12 TOF patients and 4 controls. A total of 100 TOF cases and 200 healthy controls were recruited for DNA sequencing.
  
  
  RESULTS
  The mRNA and protein expressions of the HIRA gene in the myocardium of the TOF patients were both significantly lower as compared to the controls (P < 0.05). Five single nucleotide polymorphisms (SNPs), including g.4111A>G (rs1128399), g.4265C>A (rs4585115), g.4369T>G (rs2277837), g.4371C>A (rs148516780), and g.4543T>C (rs111802956), were found in the promoter region of the HIRA gene. There were no significant differences of frequencies in these SNPs between the TOF patients and the controls (P > 0.05).
  
  
  CONCLUSIONS
  The abnormal lower expression of the HIRA gene in the myocardium may participate in the pathogenesis of TOF.
authors.affiliation: Pediatric Cardiovascular Center, Children's Hospital of Fudan University, Shanghai 201102, China.
authors.forename: Zhao-Ru
authors.initials: ZR
authors.lastname: Ju
authors.affiliation: Pediatric Cardiovascular Center, Children's Hospital of Fudan University, Shanghai 201102; Laboratory of Congenital Heart Disease, Shanghai Key Laboratory of Birth Defects, Shanghai 201102, China.
authors.forename: Hui-Jun
authors.initials: HJ
authors.lastname: Wang
authors.affiliation: Pediatric Cardiovascular Center, Children's Hospital of Fudan University, Shanghai 201102; Laboratory of Congenital Heart Disease, Shanghai Key Laboratory of Birth Defects, Shanghai 201102, China.
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Ma
authors.affiliation: Laboratory of Congenital Heart Disease, Shanghai Key Laboratory of Birth Defects, Shanghai 201102, China.
authors.forename: Duan
authors.initials: D
authors.lastname: Ma
authors.affiliation: Pediatric Cardiovascular Center, Children's Hospital of Fudan University, Shanghai 201102; Laboratory of Congenital Heart Disease, Shanghai Key Laboratory of Birth Defects, Shanghai 201102, China.
authors.forename: Guo-Ying
authors.initials: GY
authors.lastname: Huang
mesh_terms: D000483:Alleles; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005838:Genotype; D056488:Histone Chaperones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D013771:Tetralogy of Fallot / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; C086057:HIRA protein, human; D056488:Histone Chaperones; D012333:RNA, Messenger; D014157:Transcription Factors