高迁移率蛋白B1基因单核苷酸多态性对动脉瘤性蛛网膜下腔出血后迟发性脑缺血的影响

The effects of single nucleotide polymorphism of high-mobility group box-1 protein on delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage

目的探讨高迁移率蛋白B1(high-mobility group box-1 protein,HMGB1)的单核苷酸多态性(single nucleotide polymorphism,SNP)在预测动脉瘤性蛛网膜下腔出血(aneurysmal subarachnoid hemorrhage,aSAH)后迟发性脑缺血(delayed cerebral ischemia,DCI)发生的价值。方法纳入2012年1月-2015年12月本院收治的149例aSAH患者,并以50例体检健康人群为对照组,通过外周血检测HMGB1的rs2249825(3814C/G)的基因型,并通过多因素logistics回归分析确定HMGB1的rs2249825基因型与DCI发生的关系。结果 149例aSAH患者和50例健康对照组人群的HMGB1 SNP rs2249825基因型均处于哈迪温伯格平衡状态,但2组的HMGB1的rs2249825基因型频率无统计学差异(χ~2=4.091,P=0.129)。149例aSAH患者中有31例(20.8%)发生DCI,与无DCI发生的aSAH患者比较,发生DCI患者的Hunt-Hess分级≥3级(45.2%vs 16.0%,P=0.001)、脑水肿(32.3%vs 10.2%,P=0.002)、脑血管痉挛(61.3%vs 12.7%,P<0.001)、出院时mRS评分≥3分(74.2%vs 46.6%,P=0.006)、出院后90 d mRS评分≥3分(61.3%vs 32.2%,P=0.003)和HMGB1的rs2249825基因型CG或GG患者(54.8%vs 19.5%,P<0.001)比例更高。多因素logistics回归分析确定HMGB1的rs2249825基因型为CG或GG(OR=5.695,95%CI=1.804~17.975,P=0.003)、Hunt-Hess分级≥3级(OR=1.805,95%CI=1.132~2.880,P=0.013)和脑水肿(OR=2.195,95%CI=1.321~3.915,P=0.005)是影响aSAH患者发生DCI的独立危险因素。结论 HMGB1的rs2249825的次要等位基因G与aSAH患者DCI发生风险增加有关。

Objective To investigate the value of single nucleotide polymorphism(SNP) of high-mobility group box-1 protein(HMGB1) in predicting the delayed cerebral ischemia(DCI)occurrence after aneurysmal subarachnoid hemorrhage(aSAH).Methods 149 patients with aSAH admitted to our hospital were enrolled from January 2012 to December 2015, and 50 healthy subjects were selected as the control group. The genotype of HMGB1 rs2249825(3814 C/G) was detected in peripheral blood sample. Multivariate logistic regression analysis was used to determine the association of HMGB1 rs2249825 genotype with DCI.Results The HMGB1 rs2249825 genotypes in 149 patients with aSAH and 50 healthy controls were in Hardy-Weinberg equilibrium, but there was no significant difference in the frequency of HMGB1 rs2249825 genotypes between the two groups(χ~2=4.091, P=0.129). DCI occurred in 31 of 149 patients with aSAH(20.8%). Compared with aSAH patients without DCI, the Hunt-Hess grade ≥3(45.2% vs 16.0%, P=0.001), cerebral edema(32.3% vs 10.2%, P=0.002), cerebral vasospasm(61.3% vs 12.7%, P<0.001), mRS score ≥3 at discharge(74.2% vs 46.6%, P=0.006), mRS score ≥3 at 90-day post-discharge(61.3% vs 32.2%, P=0.003) and the HMGB1 rs2249825 genotypes of CG or GG(54.8% vs 19.5%, P<0.001) were significantly higher in aSAH patients with DCI. Multivariate logistic regression analysis confirmed that HMGB1 rs2249825 genotype with CG or GG(OR=5.695, 95% CI=1.804~17.975, P=0.003), Hunt-Hess grade≥3(OR=1.805, 95% CI=1.132~2.880, P=0.013) and cerebral edema(OR=2.195, 95% CI=1.321~3.915, P=0.005) were independent risk factors for DCI occurance in aSAH patients.Conclusion The secondary allele G of HMGB1 rs2249825 was associated with an increased risk of DCI in patients with aSAH.