Objectives: Ischemic stroke has long been a global health threat. Genetic factors, a looming risk for ischemic stroke, remain unexplored. The high-mobility group box 1 (HMGB1) protein showed a connection with the occurrence and development of ischemic stroke. This study was conducted to find whether frequent HMGB1 polymorphisms (rs1045411, rs1412125, and rs2249825) play a role in ischemic stroke susceptibility and recurrence risk.
Methods: Our study was carried out in a Chinese Han population with a sample size of 871 patients and 858 age-matched healthy controls. Tag single nucleotide polymorphisms (tagSNPs) were selected by conventional protocols and DNA was extracted for genotype analysis after the participants had signed an informed consent. Comprehensive statistical analyses were conducted.
Results: It was found that the C allele of the HMGB1 rs1412125 (OR = 1.263, 95% CI = 1.075-1.483, P = 0.004) and HMGB1 rs2249825 (adjusted OR = 2.464, 95% CI = 1.215-4.996, P = 0.012) variants was associated with a high risk of ischemic stroke, with the male subgroup carrying the TT allele of the HMGB1 rs1045411 variant tended to suffer more from the disease (adjusted OR = 3.600, 95% CI = 1.272-10.193, P = 0.016). A haplotype study also showed significant results (OR = 1.554, 95% CI = 1.246-1.938, P = 0.001). The rs1412125 polymorphism was highly associated with the chance of recurrence but not with the onset age (TC vs. TT: P = 0.034; CC vs. TT: P < 0.001). Cox regression analysis and stratified analysis were carried out with notable conclusions.
Conclusions: Our study provided evidence for the association between HMGB1 polymorphisms and ischemic stroke susceptibility and recurrence, indicating that HMGB1 gene variants may be potential markers for first and secondary stroke prevention.
Keywords: Single nucleotide polymorphism; high-mobility group box 1; ischemic stroke; ischemic stroke recurrence; onset age.
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