Association of Common Variants in the IL-33/ST2 Axis with Ischemic Stroke

Abstract

Background: Recent studies have reported that the levels of serum interleukin-33 (IL- 33) and its receptor, suppression of tumorigenicity 2 (ST2), are potential biomarkers for susceptibility of cardiovascular diseases. However, the genetic association of the IL-33/ST2 axis with cardiovascular diseases remains controversial. Objective: We aimed to investigate the association between common variants in the IL-33/ST2 axis and ischemic stroke in the Han Chinese population. Methods: We consecutively enrolled 1166 patients with ischemic stroke and 1079 age- and gender- matched controls. Eight single nucleotide polymorphisms (SNPs) within IL-33/ST2 axis were genotyped using the improved Multiple Ligase Detection Reaction platform. We analyzed the association between the tested SNPs and ischemic stroke at both the genotype and haplotype levels. Results: Binary logistic regression analysis indicated that rs10435816 (additive model: odds ratio [OR]=0.72, 95% confidence interval [CI], 0.54-0.95; recessive model: OR=0.72, 95%CI, 0.56- 0.94) was associated with a decreased risk of ischemic stroke after adjustment of confounding factors. Subgroup analysis indicated that rs10435816 (additive model: OR=0.61, 95%CI, 0.41-0.89; recessive model: OR=0.56, 95%CI, 0.40-0.80), rs7025417 (additive model: OR=0.57, 95%CI, 0.39-0.83), rs11792633 (additive model: OR=0.66, 95%CI, 0.46-0.95; recessive model: OR=0.67, 95%CI, 0.49-0.93), and rs7044343 (additive model: OR=0.69, 95%CI, 0.48-0.97; recessive model: OR=0.67, 95%CI, 0.49-0.91) were associated with a decreased risk of large-artery atherosclerosis stroke after adjustment of confounding factors. Conclusion: Our findings suggested an association between common variants in the IL-33/ST2 axis and a decreased risk of ischemic stroke in the Han Chinese population.

IL-33 Gene Polymorphisms as Potential Biomarkers of Disease Susceptibility and Response to TNF Inhibitors in Rheumatoid Arthritis, Ankylosing Spondylitis, and Psoriatic Arthritis Patients

“…Although, several other polymorphisms within the IL-33 gene have been shown to be significantly associated with asthma susceptibility in various populations (50). A significant relationship was also found between the IL-33 rs7044343 polymorphism and ischemic stroke in a Chinese cohort (67). On the contrary, there were no associations between the IL-33 rs7044343 polymorphism and inflammatory bowel disease or idiopathic achalasia in an Italian cohort (68,69).…”

IL‐33 as a Novel Serum Prognostic Marker of Intracerebral Hemorrhage

“…The involvement of IL-33 in the course of ischemic stroke has been widely reported. The study of Li et al pointed out that there is a correlation between the common variants of IL-33 and the reduced risk of ischemic stroke in the Chinese Han population [36]. Similarly, Li and his colleagues found that IL-33 improves ischemic brain injury by promoting Th2 response and inhibiting Th17 response [36].…”

“…The study of Li et al pointed out that there is a correlation between the common variants of IL-33 and the reduced risk of ischemic stroke in the Chinese Han population [36]. Similarly, Li and his colleagues found that IL-33 improves ischemic brain injury by promoting Th2 response and inhibiting Th17 response [36]. Interestingly, earlier studies pointed out that IL-33 could attenuate the occurrence and development of atherosclerosis by inducing IL-5 and ox-LDL antibodies [37].…”

IL-33/ST2 immunobiology in coronary artery disease: A systematic review and meta-analysis

“…Studies that did not meet these standards were excluded. Thus, seven casecontrol studies met our inclusion criteria for qualitative data analysis, and contained a total of 10686 cases and 10775 healthy subjects (7,8,(37)(38)(39)(40)(41). Two researchers simultaneously screened the studies back-to-back and obtained consistent results.…”