The human ATF1 rs11169571 polymorphism increases essential hypertension risk through modifying miRNA binding
The human ATF1 rs11169571 polymorphism increases essential hypertension risk through modifying miRNA binding
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人类 ATF1 rs11169571 多态性通过改变 miRNA 结合增加原发性高血压风险
DOI：
10.1016/j.febslet.2015.06.029
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发表时间：
2015-07
期刊：
影响因子：
--
通讯作者：
Yang P
中科院分区：
文献类型：
--
作者：
Shi K;Du B;Si D;Yang P
转录激活因子1（ATF 1）可能通过诱导NADPH氧化酶1（NOX 1）和自由基氧（ROS）的产生而参与原发性高血压（EH）的发病。在以往的基因芯片分析中发现ATF 1在EH患者中有异常表达。我们检测了位于ATF 1 3′-非翻译区（3′UTR）的单核苷酸多态性（SNP）是否通过影响microRNA（miRNA）结合而与EH易感性相关。计算机模拟分析表明，rs 11169571（T > C）是调节miRNA的候选SNP：ATF 1 mRNA复合物中，hsa-miR-1283的能量变化最大，荧光素酶报告基因分析显示miR-1283抑制了携带-T等位基因的报告基因载体的活性，而不是C等位基因此外，HA-VSMCs中miR-1283的抑制增强了ATF 1 mRNA的表达以及ROS水平。进一步的病例对照研究显示rs 11169571与EH的风险增加显著相关。最后，我们观察到与rs 11169571的TT携带者相比，CC携带者的EH患者外周血中的ATF 1蛋白水平增加，TC携带者的ATF 1水平居中。提示ATF 1基因rs 11169571位点可能与EH相关，其SNP修饰的转录后基因调控可能是EH的一个潜在发病机制。
Activating transcription factor 1 (ATF1) may be involved in essential hypertension (EH) by induction of NADPH oxidase 1 (NOX1) and radical oxygen species (ROSs) production. Abnormal expression of ATF1 was found in EH in previous microarray analysis. Here we tested whether a single nucleotide polymorphism (SNP) located in the 3′-untranslated region (3′UTR) of ATF1 was associated with EH susceptibility by affecting microRNA (miRNA) binding.In silicoanalysis indicated that rs11169571 (T > C) was a candidate SNP to modulate miRNA: ATF1 mRNA complex, with the greatest changed energy for hsa-miR-1283, and the luciferase reporter analysis showed that miR-1283 inhibited the activity of the reporter vector carrying –T allele, but not the –C allele. In addition, inhibition of miR-1283 in HA-VSMCs enhanced the expression of ATF1 mRNA as well as the ROS levels. Further case-control study showed that rs11169571 was significantly associated with increased risk of EH. Finally, we observed an increased ATF1 protein level in peripheral blood of EH patients with CC carriers compared to TT carriers of rs11169571, with an intermediate ATF1 level in TC carriers. These results suggested that rs11169571 ofATF1gene may be associated with EH, and the SNP-modified posttranscriptional gene regulation by miRNAs could be a potentially pathogenetic mechanism of EH.
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影响因子：
4.1
作者：
S. Pan;H. Naruse;T. Nakayama
通讯作者：
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影响因子：
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作者：
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作者：
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DOI：
10.1152/ajpheart.00242.2010
发表时间：
2010-09-01
影响因子：
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作者：
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Griendling, Kathy K.
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作者：
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通讯作者：
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