Department of Microbiology and Immunology, Medical College, China Three Gorges University, No.8, Da Xue Road, Yichang, 443002, Hubei Province, People's Republic of China.
The Institute of Infection and Inflammation, China Three Gorges University, Yichang, 443002, Hubei, China.
Mol Genet Genomics. 2021 Jul;296(4):799-808. doi: 10.1007/s00438-021-01782-1. Epub 2021 Apr 15.
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.
心肌梗死（MI）是冠状动脉疾病（CAD）的常见后果，也是导致全球残疾和死亡的关键因素。遗传因素促成了 CAD/MI 的发病机制，ADTRP 基因中的 SNP rs6903956 最初被发现与中国汉族人群的 CAD/MI 相关，并且在其他队列中成功得到了复制。然而，rs6903956 是否是一个功能性 SNP 以及其导致 CAD/MI 的风险机制仍不清楚。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、内皮细胞-单核细胞黏附以及血栓形成。特别是，rs6903956 的等位基因 A 与淋巴细胞中 ADTRP mRNA 水平较低有关。在本研究中，我们发现 SNP rs6903956 通过与 GATA2 相互作用表现出转录活性的等位基因差异。此外，与 G 等位基因相比，A 等位基因赋予了更大的 CAD 和 MI 风险、降低了转录活性和 GATA2 结合能力。我们的研究结果提供了有关 rs6903956 如何调节 ADTRP 表达的详细信息，可能为 CAD 病理学和易感性提供新的见解。
