HIRA Gene is Lower Expressed in the Myocardium of Patients with Tetralogy of Fallot.
HIRA Gene is Lower Expressed in the Myocardium of Patients with Tetralogy of Fallot.
复制标题
法洛四联症患者心肌中HIRA基因表达较低
DOI：
10.4103/0366-6999.191745
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发表时间：
2016-10-20
影响因子：
6.1
通讯作者：
Huang GY
中科院分区：
文献类型：
--
作者：
Ju ZR;Wang HJ;Ma XJ;Ma D;Huang GY
背景：22q11缺失综合征（22q11DS）患者最典型的心脏异常是圆锥动脉干缺损（CTD）。组蛋白细胞周期调节因子（histone cell cycle regulator，HIRA）基因作为位于22q11DS关键区域的候选基因之一，在动物模型中被报道可能与CTD相关。本研究旨在分析法洛四联症（TOF）患者HIRA基因的表达水平和启动子区潜在的DNA序列变异。研究方法：采用实时定量聚合酶链反应检测了39例TOF患者右心室流出道（RVOT）心肌组织和4例非心源性死亡儿童右心室流出道（RVOT）心肌组织的信使RNA（mRNA）表达。采用免疫组化法检测12例TOF患者和4例对照组的蛋白表达。共招募了100例TOF病例和200例健康对照进行DNA测序。结果如下：TOF患者心肌组织HIRA基因mRNA和蛋白表达均明显低于对照组（P < 0.05）。在HIRA基因启动子区发现5个单核苷酸多态性（SNP），分别为g.4111A>G（rs1128399）、g.4265C>A（rs4585115）、g.4369T>G（rs2277837）、g.4371C>A（rs148516780）和g.4543T>C（rs111802956）。TOF组与对照组的SNPs频率差异无统计学意义（P > 0.05）。结论：心肌组织中HIRA基因的异常低表达可能参与了TOF的发病过程。
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). Conclusion: The abnormal lower expression of the HIRA gene in the myocardium may participate in the pathogenesis of TOF.
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影响因子：
16
作者：
Ray-Gallet, D;Quivy, JP;Almouzni, G
通讯作者：
Almouzni, G
DOI：
10.4161/15384101.2014.967123
发表时间：
2015
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Gal C;Moore KM;Paszkiewicz K;Kent NA;Whitehall SK
通讯作者：
Whitehall SK
影响因子：
6.1
作者：
Wang Xianling;Yang Yanhui;Jia Jianping
通讯作者：
Jia Jianping
影响因子：
5.3
作者：
SHERWOOD, PW;TSANG, SVM;OSLEY, MA
通讯作者：
OSLEY, MA
影响因子：
2.6
作者：
Starr, Joanne P.
通讯作者：
Starr, Joanne P.