在法洛四联症样本中发现了ZFPM2的CpG岛岸甲基化。
CpG island shore methylation of ZFPM2 is identified in tetralogy of fallot samples.
作者信息
Sheng Wei, Chen Long, Wang Huijun, Ma Xiaojing, Ma Duan, Huang Guoying
机构信息
Children Hospital of Fudan University, Shanghai, China.
Shanghai Key Laboratory of Prevention and Intervention of Birth Defects, Shanghai, China.
出版信息
Pediatr Res. 2016 Jul;80(1):151-8. doi: 10.1038/pr.2016.42. Epub 2016 Mar 9.
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.
背景
ZFPM2基因在心脏形态发生以及心外膜冠状动脉血管发育过程中发挥重要作用，然而，关于其在法洛四联症（TOF）发病机制中的表观遗传调控知之甚少。
方法
采用MassArray（Sequenom公司，加利福尼亚州圣地亚哥）和亚硫酸氢盐测序聚合酶链反应（BSP）检测ZFPM2基因的甲基化水平。运用实时定量PCR分析TOF患者心肌中ZFPM2基因的mRNA水平。
结果
TOF患者中，ZFPM2启动子CpG岛岸区的甲基化水平显著更高，中位数为80.32%（四分位数间距（IQR）：73.54 - 85.75%，N = 42），而对照组为59.63%（IQR：44.79 - 73.83%；P = 0.0186，N = 6）。ZFPM2启动子CpG岛的甲基化状态未观察到显著差异。与对照组相比，TOF患者的ZFPM2 mRNA水平显著更低（P < 0.05）。ZFPM2的异常甲基化值与其mRNA水平的显著变化呈负相关（r = -0.40，P = 0.008，N = 42）。
结论
ZFPM2基因启动子CpG岛岸区的异常甲基化状态可能与其在TOF患者中的基因转录调控有关。
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