GATA2 regulates the CAD susceptibility gene ADTRP rs6903956 through preferential interaction with the G allele
GATA2 regulates the CAD susceptibility gene ADTRP rs6903956 through preferential interaction with the G allele
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GATA2 通过优先与 G 等位基因相互作用调节 CAD 易感基因 ADTRP rs6903956
DOI：
10.1007/s00438-021-01782-1
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发表时间：
2021-04
影响因子：
3.1
通讯作者：
Jian Yang
中科院分区：
文献类型：
--
作者：
Chunyan Luo;Bo Tang;Subo Qin;Chengfu Yuan;Youqin Du;Jian Yang
心肌梗死（MI）是冠状动脉疾病（CAD）的常见结局，是导致全球残疾和死亡的关键因素。遗传因素参与CAD/MI的发病机制，ADTRP基因中的SNP rs6903956首次在中国汉族人群中发现与CAD/MI相关，并在其他队列中成功复制。然而，rs6903956是否是功能性SNP及其对CAD/MI的风险机制尚不清楚。ADTRP基因编码的雄激素依赖性TFPI调节蛋白调节血管内皮细胞功能、内皮单核细胞粘附和血栓形成。特别是rs6903956的等位基因A与淋巴细胞中较低的ADTRP mRNA水平相关。在本研究中，我们发现SNP rs6903956通过与GATA2相互作用在转录活性上存在等位基因差异。此外，与G等位基因相比，A等位基因具有更高的冠心病和心肌梗死风险，转录活性和GATA2结合能力降低。我们的研究结果提供了rs6903956如何调节ADTRP表达的细节，并可能为CAD病理和易感性提供新的见解。
Myocardial infarction (MI) is a frequent outcome of coronary artery disease (CAD) and the key factor contributing to worldwide disability and death. Genetic factors contribute to the pathogenesis of CAD/MI, and SNP rs6903956 in the ADTRP gene was first found associated with CAD/MI in the Chinese Han population, which was successfully replicated in other cohorts. However, whether rs6903956 is a functional SNP and its risk mechanism to CAD/MI remains unknown. The ADTRP gene-encoded androgen-dependent TFPI regulating protein regulates vascular endothelial cell function, endothelial–monocyte adhesion, and thrombosis. The allele A of rs6903956, in particular, is associated with lower ADTRP mRNA levels in lymphocytes. In the current study, we found that SNP rs6903956 exhibits allelic differences in transcriptional activity by interacting with GATA2. Also, the A allele conferred a greater risk of CAD and MI, lowered transcriptional activity, and GATA2 binding ability as compared to the G allele. Our findings provide details on how rs6903956 regulates the expression of ADTRP and may provide novel insights into CAD pathology and susceptibility.
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影响因子：
20.3
作者：
Lupu, Cristina;Zhu, Hua;Lupu, Florea
通讯作者：
Lupu, Florea
影响因子：
64.8
作者：
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Wang, Q
影响因子：
20.3
作者：
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影响因子：
3.7
作者：
Guo CY;Gu Y;Li L;Jia EZ;Li CJ;Wang LS;Yang ZJ;Cao KJ;Ma WZ
通讯作者：
Ma WZ
DOI：
--
发表时间：
2017-05
期刊：
Arteriosclerosis, Thrombosis, and Vascular Biology
影响因子：
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作者：
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