EDNRA affects susceptibility to large artery atherosclerosis stroke through potential inflammatory pathway

Area of Science:

• Genetics
• Immunology
• Cardiovascular Research

Background:

• Large artery atherosclerotic stroke (LAA) is a significant health concern.
• The role of Endothelin type A receptor (EDNRA) genetic polymorphisms in LAA susceptibility is not fully understood.
• Inflammation is implicated in the pathogenesis of atherosclerosis and stroke.

Purpose of the Study:

• To investigate the association between EDNRA genetic polymorphisms and LAA risk in a Han Chinese population.
• To explore the involvement of inflammation, specifically the NLRP3 pathway, in this association.
• To analyze the correlation between EDNRA gene expression, inflammatory markers, and LAA.

Main Methods:

• Genotyping of 16 single nucleotide polymorphisms (SNPs) in EDNRA using case-control association analysis.
• Quantification of EDNRA and NLRP3 mRNA and protein levels.
• Measurement of inflammatory cytokine concentrations (TNFα, IL-1β, IL-6, IL-10, IL-18, CCL18) in peripheral blood.
• Correlation analysis between SNPs, gene expression, and inflammatory markers.

Main Results:

• The rs5343 TT genotype of EDNRA was significantly associated with an increased risk of LAA (OR=3.243, P=0.001).
• NLRP3 upregulation and elevated levels of IL-10, IL-18, and CCL-18 were observed in LAA patients compared to controls.
• EDNRA polymorphisms correlated with NLRP3, IL-6, IL-10, and IL-18 levels.
• Positive correlations were found between EDNRA transcription and NLRP3 transcript levels (r=0.437, p<0.001) and IL-18 concentrations (r=0.212, p<0.001).

Conclusions:

• EDNRA genetic variations are linked to susceptibility to large artery atherosclerotic stroke.
• The NLRP3-mediated inflammatory pathway may contribute to the association between EDNRA and LAA.
• These findings highlight EDNRA as a potential genetic factor and therapeutic target in LAA.