DNA methylation status of NKX2-5, GATA4 and HAND1 in patients with tetralogy of fallot

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• 作者：Wei Sheng (1) (3)
  Yanyan Qian (2)
  Huijun Wang (1) (3)
  Xiaojing Ma (1) (3)
  Ping Zhang (3)
  Lianwei Diao (5)
  Quan An (5)
  Long Chen (4)
  Duan Ma (2) (3)
  Guoying Huang (1) (3)
  
• 关键词：DNA methylation ; NKX2 ; 5 ; GATA4 and HAND1 genes ; Tetralogy of fallot
• 刊名：BMC Medical Genomics
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：6
• 期：1
• 全文大小：1,072 KB
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  36. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1755-8794/6/46/prepub
  
• 作者单位：Wei Sheng (1) (3)
  Yanyan Qian (2)
  Huijun Wang (1) (3)
  Xiaojing Ma (1) (3)
  Ping Zhang (3)
  Lianwei Diao (5)
  Quan An (5)
  Long Chen (4)
  Duan Ma (2) (3)
  Guoying Huang (1) (3)
  
  1. Children Hospital of Fudan University, Shanghai, 201102, China
  3. Shanghai Key Laboratory of Prevention and Intervention of Birth Defects, Shanghai, 201102, China
  2. Key Laboratory of Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, 20003, China
  5. Wuhe Chinese Medicine Hospital, Wuhe, 233300, China
  4. Department of Forensic Medicine, Fudan University, Shanghai, 20003, China
  
• ISSN：1755-8794

文摘

Background NKX2-5, GATA4 and HAND1 are essential for heart development, however, little is known regarding their epigenetic regulation in the pathogenesis of tetralogy of fallot (TOF). Methods Methylation levels were measured in three regions of NKX2-5 (M1: -1596?bp?~-1374?bp, M2: -159?bp?~-17?bp and M3: 1058?bp?~-524?bp), one region of GATA4 (M: -392?bp?~-07?bp) and three regions of HAND1 (M1: -887?bp?~-414?bp, M2: -436?bp?~-?bp and M3: 37?bp?~-98?bp) using the Sequenom MassARRAY platform. QRT-PCR was used to analyze NKX2-5 and HAND1 mRNA levels in the right ventricular myocardium of TOF patients. Results TOF patients had a significantly higher NKX2-5_M3 median methylation level than controls (41.65% vs. 22.18%; p--.0074; interquartile range [IQR]: 30.46%-3.35%, N--0 and 20.07%-4.31%, N--; respectively). The HAND1_M1 median methylation level was also significantly higher in TOF patients than controls (30.05% vs. 17.54%; p--.0054; IQR: 20.77%-0.89%, N--0 and IQR: 14.69%-0.64%; N--; respectively). The methylation statuses of NKX2-5_M1, NKX2-5_M2, GATA4_M, HAND1_M2 or HAND1_M3 were not significantly different in TOF patients compared to controls. The methylation values for NKX2-5_M3 were negatively correlated with mRNA levels (r-- 0.463, p--.010, N--0) and there was a significant association between HAND1_M1 methylation status and mRNA levels (r-- 0.524, p--.003, N--0) in TOF patients. Conclusions Aberrant methylation statuses of the NKX2-5 gene body and HAND1 promoter regions are associated with the regulation of gene transcription in TOF patients and may play an important role in the pathogenesis of TOF.