Genes and outcome after aneurysmal subarachnoid haemorrhage

• Published in: Journal of neurology Vol. 252; no. 4; pp. 417 - 422
• Main Authors: RUIGROK, Y. M, SLOOTER, A. J. C, BARDOEL, A, FRIJNS, C. J. M, RINKEL, G. J. E, WIJMENGA, C
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01-04-2005; Springer Nature B.V
• Subjects: Aged; Apolipoproteins E - genetics; Biological and medical sciences; Cardiovascular system; Female; Gene Expression Regulation - physiology; Gene Frequency; Genotype; Glasgow Outcome Scale; Humans; Insulin-Like Growth Factor I - genetics; Male; Medical sciences; Middle Aged; Neurology; Odds Ratio; Outcome Assessment (Health Care); Pharmacology. Drug treatments; Polymorphism, Genetic; Prognosis; Retrospective Studies; Risk; Subarachnoid Hemorrhage - epidemiology; Subarachnoid Hemorrhage - genetics; Tumor Necrosis Factor-alpha - genetics; Vascular diseases and vascular malformations of the nervous system; Vasodilator agents. Cerebral vasodilators; Vascular disease; Nervous system diseases; Prognosis; Subarachnoid hemorrhage; Aneurysm; Cardiovascular disease; subarachnoid haemorrhage; polymorphisms; outcome; Polymorphism
• ISSN: 0340-5354; 1432-1459
• DOI: 10.1007/s00415-005-0661-y

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.
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.
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 epsilon4 OR 0.4, 95% CI 0.1-1.2; APOE epsilon2 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.
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.