Genes and outcome after aneurysmal subarachnoid haemorrhage
Genes and outcome after aneurysmal subarachnoid haemorrhage
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DOI：
10.1007/s00415-005-0661-y
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发表时间：
2005-04-01
影响因子：
6
通讯作者：
Wijmenga, C
中科院分区：
文献类型：
--
作者：
Ruigrok, YM;Slooter, AJC;Wijmenga, C
目的蛛网膜下腔出血（SAH）后早期和继发性脑缺血是影响预后的重要因素。脑缺血是可能影响恢复的基因表达的有力刺激。我们研究了载脂蛋白E（APOE）、胰岛素样生长因子-1（IGF-1）、肿瘤坏死因子-A（TNF-A）、白细胞介素-1A（IL-1A）、白细胞介素-1B（IL-1B）和白细胞介素-6（IL-6）基因的功能多态性是否与蛛网膜下腔出血后的预后相关。方法对167例原发性蛛网膜下腔出血患者进行基因分型。预后不良的风险用logistic回归分析，调整了SAH后预后的预后因素，使用野生型等位基因的纯合子作为参考。结果携带任何IGF-1非野生型等位基因的患者预后不良的风险较低（OR 0.4，95% CI 0.2 - 1.0），而携带TNF-A非野生型等位基因的患者预后不良的风险较高（OR 2.3，95% CI 1.0 - 5.4）。我们无法证明APOE与预后的相关性（APOE epsilon 4 OR 0.4，95%CI 0.1 - 1.2; APOE β 2 OR 0.7，95% CI 0.2 - 2.4）、IL-1A（OR 1.8，95% CI 0.8 - 4.0）、IL-1B（OR 0.7，95% CI 0.3 - 1.5）和IL-6（OR 0.7，95% CI 0.3 - 1.8）多态性。结论脑缺血后某些基因表达的变化可能部分解释了蛛网膜下腔出血患者预后的巨大差异。IGF-1野生型等位基因纯合子或TNF-A非野生型等位基因携带者的SAH患者预后不良的风险较高。需要在其他人群中进行额外的研究，以评估我们结果的普遍性。
Objectives Initial and secondary ischaemia are important determinants of outcome after subarachnoid haemorrhage (SAH). Cerebral ischaemia is a potent stimulus for expression of genes that may influence recovery. We investigated whether functional polymorphisms in the apolipoprotein E ( APOE), insulin-like growth factor-1 (IGF-1), tumor necrosis factor-A (TNF-A), interleukin-1A (IL-1A), interleukin-1B (IL-1B), and interleukin-6 (IL-6) genes are related with outcome after aneurysmal SAH. Methods Genotyping of the polymorphisms was performed in a consecutive series of 167 patients with aneurysmal SAH. The risk of a poor outcome was analysed with logistic regression with adjustment for prognostic factors for outcome after SAH, using the homozygotes for the wild type alleles as a reference. Results Patients carrying any IGF-1 non-wild type allele had a lower risk of a poor outcome ( OR 0.4, 95% CI 0.2 - 1.0), while carriers of the TNF-A non-wild type allele had a higher risk ( OR 2.3, 95% CI 1.0 - 5.4). We could not demonstrate an association with outcome for APOE ( APOE epsilon 4 OR 0.4, 95% CI 0.1 - 1.2; APOE epsilon 2 OR 0.7, 95% CI 0.2 - 2.4), IL-1A ( OR 1.8, 95% CI 0.8 - 4.0), IL-1B ( OR 0.7, 95% CI 0.3 - 1.5) and IL-6 ( OR 0.7, 95% CI 0.3 - 1.8) polymorphisms. Conclusions Variation in some genes that are expressed after cerebral ischaemia may partly explain the large differences in outcome between patients with aneurysmal SAH. SAH patients homozygote for the IGF-1 wild type allele or carriers of the TNF-A non-wild type allele have a higher risk of poor outcome. Additional studies in other populations are needed to assess the generalisability of our results.