AUTHOR=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 

TITLE=Single-Nucleotide Polymorphisms in the 3' Untranslated Region of CORIN Associated With Cardiovascular Diseases in a Chinese Han Population: A Case–Control Study

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 8 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2021.625072

DOI=10.3389/fcvm.2021.625072

ISSN=2297-055X

ABSTRACT=Background Corin is a transmembrane serine protease which activates pro-forms of atrial and brain natriuretic peptides. Numerous studies indicate that corin plays an important role in cardiovascular diseases (CVDs). However, there have been few studies about the correlation between single nucleotide polymorphisms (SNPs) in 3’ untranslated region (3’UTR) of CORIN and CVDs. The aims of this study were to investigate the associations of three SNPs in 3’UTR of CORIN with CVDs, and to find the seed regions of micro RNAs (miRNAs) that bind to SNPs of CORIN.
Methods and Results A case-control study (n=3537) 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 EH-control study, rs3749585T was significantly associated with the risk of EH after adjusting for sex and age in allelic (Padj=0.049) and dominant (Padj=0.015) models. Rs4695253T was significantly associated with the risk of EH in the recessive model after adjusting for sex and age (Padj=0.005). Rs3749585T was significantly and negatively associated with AF in the dominant and additive models after adjusting for sex, age, EH, HF, T2DM and CAD (dominant: Padj=0.009; additive: Padj=0.048). In 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 (Padj>0.05). The levels of high-density lipoprotein (HDL) and total cholesterol (TC) in rs4695253CC+CT were lower than the levels of HDL in rs4695253TT (42.47±10.30 vs. 48.0±10.24mg/dl, Padj=0.008; 164.01±49.15 vs. 180.81±43.92 mg/dl, Padj=0.036 ).  Luciferase assay revealed that the relative luciferase activity of rs3749585CC- transfected cells was significantly decreased by miR-494-3p, in comparison to cells transfected with rs3749585TT (P<0.001). A significant decrease in the relative luciferase activity of rs3749585TT reporter was observed as compared with rs3749585CC reporter in the presence of miR-1323 or miR-548o-3p (P=0.017 and 0.012, respectively). 
Conclusions We found significant associations between rs3749585T, rs4695253T and EH, rs4695253T and the levels of TC and HDL, rs3749585T and AF. Hsa-miR-494-3p may serve as a potential therapeutic target for EH and AF patients in the future.