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

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.

Analysis of Inflammation-Related Genes in Patients with Stanford Type A Aortic Dissection

“…Additionally, the upregulation of MYC begins earlier than clinical characteristics [ 22 ]. Interleukin-1 receptor 1 ( IL1R1 ) coding variant was related to TAAD risk through the accumulation of tumorigenicity 2 receptor (ST2) that may induce inflammatory reactions of the aorta and systemic blood vessels, leading to blood vessel damage in the smooth muscle cells (SMCs) [ 23 ]. In our study, IL1R1 and MYC also showed a high diagnostic value and positive correlation with TAAD.…”

Diagnostic and prognostic value of serum soluble suppression of tumorigenicity-2 in heart failure with preserved ejection fraction: A systematic review and meta-analysis

“…Serum sST2 is unaffected by potential confounding variables, including age, sex, body mass index, and comorbidities such as renal disease and diabetes ( 41 ), making it a promising biomarker. Relevant clinical investigations have confirmed that serum sST2 can be utilized as an additional parameter for the diagnosis and prognosis of cardiovascular illnesses such as coronary heart disease ( 42 , 43 ), aortic dissection ( 44 , 45 ), and HF ( 46 , 47 ).…”

Zero risk is not possible in emergency medicine

“…In the future, biomarkers for screening may offer a solution. For AD assessment, widespread use of the d ‐dimer levels is limited by low specificity, but newer biomarkers such as Aggrecan, IL1R1 and soluble ST2 have shown some potential in pre‐clinical studies 5,6 . Other potential targets include biomarkers from the aortic extracellular matrix such as metalloproteinases, TGF‐β, elastin fragments and those associated with vascular smooth muscle 7 .…”

“…For AD assessment, widespread use of the D-dimer levels is limited by low specificity, but newer biomarkers such as Aggrecan, IL1R1 and soluble ST2 have shown some potential in pre-clinical studies. 5,6 Other potential targets include biomarkers from the aortic extracellular matrix such as metalloproteinases, TGF-β, elastin fragments and those associated with vascular smooth muscle. 7 Similarly, micro RNAs (non-coding, small RNA sequences that are stable and detectable in circulating blood) show promise, but all are a long way from demonstrated diagnostic utility in humans.…”