El Husseini Nada, Hoffman Benjamin M, Bennett Ellen R, Li Yen-Wei, Williamson Taylor Rachel A, Hailey Claire E, Richardson Kara, Li Yi-Ju, Laskowitz Daniel T, James Michael L
Department of Neurology, Duke University, Durham, North Carolina; Department of Neurology, Wake Forest Baptist Medical Center, Winston Salem, North Carolina.
Department of Neurology, Wake Forest Baptist Medical Center, Winston Salem, North Carolina.
J Stroke Cerebrovasc Dis. 2018 Jan;27(1):125-131. doi: 10.1016/j.jstrokecerebrovasdis.2017.08.017. Epub 2017 Sep 28.
Genes associated with the inflammatory response and cytostructural integrity may influence recovery following a brain injury. To examine this in the setting of spontaneous intracerebral hemorrhage (ICH), selected single nucleotide polymorphisms (SNPs) were assessed for associations with patient outcome.
A cohort of 54 patients with supratentorial ICH were enrolled. Based on known involvement with neuroinflammation and cytostructural integrity, 10 preselected SNPs from 6 candidate genes were tested for associations with 6-month functional outcome (modified Rankin Scale [mRS] ≥ 3), mortality, and in-hospital deterioration (Glasgow Coma Scale decrease by >2 within 7 days of admission) following ICH. Fisher's exact test and logistic regression with adjustment for race and ICH score were performed.
SNP rs10940495 (gp130 G/A) within the gp130 gene was the only SNP significantly associated with lower odds of an unfavorable 6-month functional outcome (odds ratio = .16 for mRS ≥ 3; 95% confidence interval, .03-.87, P = .03). Compared with major allele (A) homozygotes, minor allele (G) carriers in the IL6 signal transducer gene (gp130) locus were 84% less likely to have a poor outcome (mRS ≥ 3) at 6 months following spontaneous ICH. The SNP rs10940495 (gp130 G/A) and SNP rs3219119 (PARP-1 A/T) were associated with 6-month mortality (P = .02 and .04, respectively) only on univariate analysis. None of the SNPs examined were associated with in-hospital deterioration.
In this exploratory study, SNP rs10940495 in the gp130 locus was associated with functional outcome at 6 months following spontaneous ICH. These findings, which should be validated through a larger study, suggest that inflammation plays an important role in mediating outcomes after ICH.
与炎症反应和细胞结构完整性相关的基因可能会影响脑损伤后的恢复情况。为了在自发性脑出血(ICH)的背景下对此进行研究,我们评估了选定的单核苷酸多态性(SNP)与患者预后的相关性。
纳入了一组54例幕上ICH患者。基于已知的与神经炎症和细胞结构完整性的关联,对来自6个候选基因的10个预选SNP进行检测,以确定其与ICH后6个月功能预后(改良Rankin量表[mRS]≥3)、死亡率和住院期间病情恶化(入院7天内格拉斯哥昏迷量表下降>2)的相关性。进行了Fisher精确检验以及对种族和ICH评分进行调整的逻辑回归分析。
gp130基因内的SNP rs10940495(gp130 G/A)是唯一与6个月功能预后不良几率显著相关的SNP(mRS≥3时比值比=0.16;95%置信区间,0.03 - 0.87,P = 0.03)。与主要等位基因(A)纯合子相比,IL6信号转导基因(gp130)位点的次要等位基因(G)携带者在自发性ICH后6个月出现不良预后(mRS≥3)的可能性低84%。SNP rs10940495(gp130 G/A)和SNP rs3219119(PARP - 1 A/T)仅在单因素分析中与6个月死亡率相关(分别为P = 0.02和0.04)。所检测的SNP均与住院期间病情恶化无关。
在这项探索性研究中,gp130位点的SNP rs10940495与自发性ICH后6个月的功能预后相关。这些发现应通过更大规模的研究进行验证,提示炎症在ICH后介导预后方面起重要作用。