Association of IL1R1 Coding Variant With Plasma-Level Soluble ST2 and Risk of Aortic Dissection.

Wenxi Jiang,Meiyu An,Jie Du,Rong Hu,Pei Gao,Junming Zhu,Ke Lu,Wang Pei,Fengjuan Li,Xi Li,Xin Tan,Yongliang Zhong,Yuan Wang,Xue Wang,Shuai Zheng

doi:10.3389/fcvm.2021.710425

Abstract

Objective: Aortic dissection (AD) is characterized by an acute onset, rapid progress, and high mortality. Levels of soluble ST2 (sST2) on presentation are elevated in patients with acute AD, which can be used to discriminate AD patients from patients with chest pain. sST2 concentrations were found to be highly heritable in the general population. The aim of this study was to investigate the associations of variations in ST2-related gene expression with sST2 concentrations and AD risk.Methods: This case-control study involving a total of 2,277 participants were conducted, including 435 AD patients and age- and sex-matched 435 controls in the discovery stage, and 464 patients and 943 controls in the validation stage. Eight ST2-related genes were selected by systematic review. Tag single-nucleotide polymorphisms (SNPs) were screened out from the Chinese population of the 1,000 Genomes Database. Twenty-one ST2-related SNPs were genotyped, and plasma sST2 concentrations were measured.Results: In the discovery stage, rs13019803 located in IL1R1 was significantly associated with AD after Bonferroni correction (p = 0.0009) and was correlated with circulating sST2 levels in patients with type A AD(AAD) [log-sST2 per C allele increased by 0.180 (95%) CI: 0.002 – 0.357] but not in type B. Combining the two stages together, rs13019803C was associated with plasma sST2 level in AAD patients [log-sST2 increased by 0.141 (95% CI: 0.055–0.227) for per C allele]. Odds ratio of rs13019803 on the risk of AAD is 1.67 (95% CI: 1.33–2.09).Conclusions: The IL1R1 SNP rs13019803C is associated with higher sST2 levels and increased risk of AAD.

Highlights

Aortic dissection (AD) is an important cause of cardiovascular death characterized by acute onset and rapid progress with poor prognosis and high mortality [1]
In the discovery stage, rs13019803 located in IL1R1 was significantly associated with AD after Bonferroni correction (p = 0.0009) and was correlated with circulating soluble ST2 (sST2) levels in patients with type A AD(AAD) [log-sST2 per C allele increased by 0.180 (95%) confidence interval (CI): 0.002 – 0.357] but not in type B
Combining the two stages together, rs13019803C was associated with plasma sST2 level in AAD patients [log-sST2 increased by 0.141 for per C allele]

Summary

Introduction

Aortic dissection (AD) is an important cause of cardiovascular death characterized by acute onset and rapid progress with poor prognosis and high mortality [1]. Acute AD is a fatal clinical emergency, with an untreated mortality rate of 1–2% per hour after symptom onset and almost 50% in the first week [2]. Identifying those members of the population with higher risk to AD is very important. Soluble (s)ST2 is regulated by vascular injury and is rapidly secreted into the circulation after stress and pro-inflammatory stimulation. We have used it to discriminate acute AD from other diseases presenting with acute chest pain [8]. In the early stages of AD, sST2 elevated levels reflect the degree of vascular injury [9, 10]. sST2 participates in adverse remodeling of blood vessels by stimulating expression of type I collagen, fibronectin, and profibrotic factors [11]

Methods

Results

Conclusion