Zhao Yichang, Yuan Xiaoyang, Zhong Yang, Zhang Yutao, Zhang Shushan, Li Sisi, Zhao Yuanyuan, Zheng Wenjun, Liu Jinqiu, Xia Yunlong, Yang Yanzong, Liu Ying, Chen Feifei
Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
Department of Clinical Laboratory, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
Front Cardiovasc Med. 2021 Aug 2;8:625072. doi: 10.3389/fcvm.2021.625072. eCollection 2021.
Corin is a transmembrane serine protease that activates pro-forms of atrial and brain natriuretic peptides. Numerous studies have indicated that corin played an important role in cardiovascular diseases (CVDs). However, there have been few studies about the correlation between single-nucleotide polymorphisms (SNPs) in the 3' untranslated region (3'UTR) of and CVDs. The aims of this study were to investigate the associations of three SNPs (rs3749585, rs4695253, and rs12641823) in the 3'UTR of with CVDs and to find the seed regions of microRNAs (miRNAs) that bind to SNPs of . A case-control study ( = 3,537) was performed in a Han population of northeastern China. CVDs included essential hypertension (EH), atrial fibrillation (AF), heart failure (HF), and coronary artery disease (CAD). Genotyping was performed using high-resolution melt analysis. In the EH-control study, rs3749585 was significantly associated with the risk of EH after adjusting for sex and age in allelic ( = 0.049; : 1.113) and dominant ( = 0.015, : 1.233) models. Rs4695253 was significantly associated with the risk of EH in the recessive model after adjusting for sex and age ( = 0.005, : 2.084). Rs3749585 was significantly and negatively associated with AF in the dominant and additive models after adjusting for sex, age, EH, HF, T2DM, and CAD (dominant: = 0.009, : 0.762; additive: = 0.048, : 0.873). In the HF-control study and CAD-control study, none of the three SNPs was associated with HF and CAD after adjusting for covariates in any models ( > 0.05). The levels of high-density lipoprotein (HDL) in rs4695253 were lower than the levels of HDL in rs4695253 (42.47 ± 10.30 vs. 48.0 ± 10.24 mg/dl, = 0.008). The levels of total cholesterol (TC) in rs4695253 were lower than the levels of TC in rs4695253 (164.01 ± 49.15 vs. 180.81 ± 43.92 mg/dl, = 0.036). Luciferase assay revealed that the relative luciferase activity of rs3749585-transfected cells was significantly decreased by miR-494-3p, in comparison to cells transfected with rs3749585 ( < 0.001). A significant decrease in the relative luciferase activity of rs3749585 reporter was observed as compared with rs3749585 reporter in the presence of miR-1323 or miR-548o-3p ( = 0.017 and 0.012, respectively). We found significant associations between rs3749585 and rs4695253 and EH, between rs4695253 and the levels of TC and HDL, and between rs3749585 and AF. Hsa-miR-494-3p may serve as a potential therapeutic target for EH and AF patients in the future.
Corin是一种跨膜丝氨酸蛋白酶，可激活心房利钠肽和脑利钠肽的前体形式。大量研究表明，Corin在心血管疾病（CVDs）中发挥着重要作用。然而，关于其3'非翻译区（3'UTR）单核苷酸多态性（SNPs）与CVDs之间的相关性研究较少。本研究旨在探讨其3'UTR中三个SNP（rs3749585、rs4695253和rs12641823）与CVDs的关联，并寻找与Corin SNPs结合的微小RNA（miRNAs）的种子区域。在中国东北汉族人群中进行了一项病例对照研究（n = 3537）。CVDs包括原发性高血压（EH）、心房颤动（AF）、心力衰竭（HF）和冠状动脉疾病（CAD）。采用高分辨率熔解分析进行基因分型。在EH与对照的研究中，在等位基因（P = 0.049；OR：1.113）和显性（P = 0.015，OR：1.233）模型中，调整性别和年龄后，rs3749585与EH风险显著相关。在调整性别和年龄后的隐性模型中，rs4695253与EH风险显著相关（P = 0.005，OR：2.084）。在调整性别、年龄、EH、HF、2型糖尿病（T2DM）和CAD后，rs3749585在显性和加性模型中与AF显著负相关（显性：P = 0.009，OR：0.762；加性：P = 0.048，OR：0.873）。在HF与对照的研究以及CAD与对照的研究中，在任何模型中调整协变量后，三个SNP均与HF和CAD无关（P > 0.05）。rs4695253中高密度脂蛋白（HDL）水平低于rs4695253中的HDL水平（42.47±10.30 vs. 48.0±10.24 mg/dl，P = 0.008）。rs4695253中总胆固醇（TC）水平低于rs4695253中的TC水平（164.01±49.15 vs. 180.81±43.92 mg/dl，P = 0.036）。荧光素酶测定显示，与转染rs3749585的细胞相比，miR - 494 - 3p显著降低了转染rs3749585细胞的相对荧光素酶活性（P < 0.001）。在存在miR - 1323或miR - 548o - 3p的情况下，与rs3749585报告基因相比，rs3749585报告基因的相对荧光素酶活性显著降低（分别为P = 0.017和0.012）。我们发现rs3749585和rs4695253与EH之间、rs4695253与TC和HDL水平之间以及rs3749585与AF之间存在显著关联。Hsa - miR - 494 - 3p未来可能成为EH和AF患者的潜在治疗靶点。
