Hong Eun Pyo, Han Sung Woo, Kim Bong Jun, Youn Dong Hyuk, Rhim Jong Kook, Jeon Jin Pyeong, Park Jeong Jin
Institute of New Frontier Research, Hallym University College of Medicine, Chuncheon 24254, Republic of Korea.
Department of Neurosurgery, Jeju National University College of Medicine, Jeju 63241, Republic of Korea.
Brain Sci. 2024 Sep 26;14(10):969. doi: 10.3390/brainsci14100969.
We investigated the effect of high mobility group box 1 (HMGB1) on intracranial aneurysms (IAs) by analyzing single-nucleotide polymorphisms (SNPs) based on genome-wide association study (GWAS) data. HMGB1 mRNA and protein expression levels in plasma were also analyzed. : This study was a comprehensive analysis of a GWAS dataset, including 250 patients with IAs and 294 controls. The HMGB1 gene region was targeted within SNP rs3742305 ± 10 kbp. Multivariate logistic regression analysis determined its association with IAs after adjusting for relevant clinical factors. HMGB1 mRNA expression was analyzed in the plasma of 24 patients selected from the GWAS dataset. The HMGB1 protein was analyzed by Western blotting. A total of seven polymorphisms, including rs1360485, rs185382445, rs2039338, rs1045411, rs3742305, rs2249825, and rs189034241, were observed. Two SNPs, including rs1045411 (UTR-3) and rs3742305 (intron), showed strong linkage disequilibrium (r = 0.99). However, none of the seven SNPs associated with IAs had an adjusted -value of < 0.0016 on multiple comparison analysis. HMGB1 mRNA levels (2) did not differ significantly between patients with IAs and the control subjects [1.07 (1.00-1.15) in patients with IAs vs. 1.05 (0.94-1.12) in controls; = 0.67)]. Also, no significant difference in the degree of plasma HMGB1 protein expression was seen between the two groups ( = 0.82). The number of SNPs associated with HMGB1 and the degree of HMGB1 mRNA and protein expression were not significantly different between patients diagnosed with IAs and the controls.
我们通过基于全基因组关联研究（GWAS）数据的单核苷酸多态性（SNP）分析，研究了高迁移率族蛋白B1（HMGB1）对颅内动脉瘤（IAs）的影响。同时还分析了血浆中HMGB1的mRNA和蛋白表达水平。本研究是对一个GWAS数据集的综合分析，包括250例颅内动脉瘤患者和294例对照。HMGB1基因区域的目标是SNP rs3742305±10 kbp范围内。多因素逻辑回归分析在调整相关临床因素后确定其与颅内动脉瘤的关联。从GWAS数据集中选取24例患者的血浆分析HMGB1 mRNA表达。通过蛋白质印迹法分析HMGB1蛋白。共观察到7个多态性位点，包括rs1360485、rs185382445、rs2039338、rs1045411、rs3742305、rs2249825和rs189034241。其中两个SNP，包括rs1045411（UTR-3）和rs3742305（内含子），显示出强连锁不平衡（r=0.99）。然而，在多重比较分析中，与颅内动脉瘤相关的7个SNP中，没有一个校正P值<0.0016。颅内动脉瘤患者和对照受试者之间的HMGB1 mRNA水平（2）没有显著差异[颅内动脉瘤患者为1.07（1.00-1.15），对照为1.05（0.94-1.12）；P=0.67]。此外，两组之间血浆HMGB1蛋白表达程度也没有显著差异（P=0.82）。在诊断为颅内动脉瘤的患者和对照之间，与HMGB1相关的SNP数量以及HMGB1 mRNA和蛋白表达程度没有显著差异。
