Genes and outcome after aneurysmal subarachnoid haemorrhage

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 (APOE4 OR 0.4, 95% CI 0.1–1.2; APOE 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.