Target Gene-Based Association Study of High Mobility Group Box Protein 1 in Intracranial Aneurysms in Koreans

Area of Science:

• Genetics
• Molecular Biology
• Neurology

Background:

• Intracranial aneurysms (IAs) are a significant cause of subarachnoid hemorrhage.
• High mobility group box 1 (HMGB1) is implicated in various inflammatory and vascular diseases.
• The role of HMGB1 in IA pathogenesis remains unclear.

Purpose of the Study:

• To investigate the association between high mobility group box 1 (HMGB1) gene single-nucleotide polymorphisms (SNPs) and intracranial aneurysms (IAs).
• To analyze HMGB1 mRNA and protein expression levels in plasma of IA patients and controls.

Main Methods:

• Genome-wide association study (GWAS) data from 250 IA patients and 294 controls were analyzed for HMGB1 SNPs.
• Multivariate logistic regression was used to assess SNP association with IAs.
• HMGB1 mRNA and protein expression were quantified in plasma samples using RT-qPCR and Western blotting, respectively.

Main Results:

• Seven HMGB1 polymorphisms were identified, with two SNPs (rs1045411 and rs3742305) showing strong linkage disequilibrium.
• No significant association was found between the analyzed HMGB1 SNPs and IAs after multiple comparison correction.
• Plasma HMGB1 mRNA and protein levels did not significantly differ between IA patients and control subjects.

Conclusions:

• Genetic variations in HMGB1 are not significantly associated with the risk of developing intracranial aneurysms.
• HMGB1 mRNA and protein expression levels in plasma do not differ between patients with IAs and healthy controls.
• These findings suggest HMGB1 may not play a critical role in the pathogenesis of intracranial aneurysms.