Genes and outcome after aneurysmal subarachnoid haemorrhage.
OBJECTIVE
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 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.


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.
Ruigrok
Y M
YM
Dept. of Neurology, Rudolf Magnus Institute of Neuroscience University Medical Centre Utrecht, 85500, 3500 GA Utrecht, The Netherlands. ij.m.ruigrok@neuro.azu.nl
Slooter
A J C
AJ
Bardoel
A
A
Frijns
C J M
CJ
Rinkel
G J E
GJ
Wijmenga
C
C
D000368:Aged; D001057:Apolipoproteins E / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D005787:Gene Frequency; D005838:Genotype; D023261:Glasgow Outcome Scale; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D017063:Outcome Assessment, Health Care; D011110:Polymorphism, Genetic; D011379:Prognosis; D012189:Retrospective Studies; D012306:Risk; D013345:Subarachnoid Hemorrhage / Q000453:epidemiology / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D001057:Apolipoproteins E; D014409:Tumor Necrosis Factor-alpha; D007334:Insulin-Like Growth Factor I
Lancet. 1991 May 11;337(8750):1158-9
1674030
J Neurosurg. 1990 Jul;73(1):37-47
2191091
Stroke. 1996 Sep;27(9):1682-7
8784149
J Clin Invest. 1998 Oct 1;102(7):1369-76
9769329
Stroke. 1988 Oct;19(10 ):1250-6
3176085
Lancet. 1995 Aug 26;346(8974):575
7658797
J Cereb Blood Flow Metab. 2001 Oct;21(10):1199-207
11598497
Cytokine Growth Factor Rev. 1999 Jun;10 (2):119-30
10743503
Nat Med. 1995 Sep;1(9):852
7585199
Diabetes. 2001 Mar;50(3):637-42
11246885
Stroke. 1990 Aug;21(8):1156-61
2389295
Neurosci Lett. 1996 Oct 25;218(1):41-4
8939476
Ann N Y Acad Sci. 2002 Nov;977:468-75
12480787
Brain Res Mol Brain Res. 1998 Aug 31;59(2):119-34
9729323
Stroke. 1997 Jun;28(6):1233-44
9183357
Neurobiol Dis. 1997;4(3-4):201-14
9361296
Stroke. 2002 Feb;33(2):548-52
11823668
Hum Mutat. 1994;4(3):178-94
7833947
Diabetes. 2002 Jul;51(7):2313-6
12086966
Eur J Clin Invest. 1992 Jun;22(6):396-402
1353022
Neurology. 1999 Dec 10;53(9):2176-9
10599801
Hum Mol Genet. 1999 Aug;8(8):1443-9
10400991
Stroke. 2001 May;32(5):1181-4
11340230
Arthritis Rheum. 1995 Feb;38(2):221-8
7848312
Nat Med. 1996 Jul;2(7):788-94
8673925
J Cereb Blood Flow Metab. 2000 Jul;20(7):1011-32
10908035
Stroke. 1994 Jul;25(7):1342-7
8023347
J Cereb Blood Flow Metab. 2000 Mar;20(3):513-9
10724116
Neurosurgery. 1988 Apr;22(4):654-61
3287211
Brain Res. 2000 Mar 24;859(2):381-5
10719091
J Neurosurg. 1982 Dec;57(6):765-8
7143058
Neuroscientist. 2002 Jun;8(3):268-75
12061506
Arch Neurol. 2000 Oct;57(10 ):1480-4
11030801
Lancet. 1997 Oct 11;350(9084):1069-71
10213549
Prog Neurobiol. 2002 Jun;67(2):161-72
12126659
J Neurosurg. 1988 Jun;68(6):985-6
3131498
J Clin Endocrinol Metab. 1998 Jul;83(7):2286-90
9661596
Neurology. 1999 Jan 15;52(2):244-8
9932938
Lancet. 1975 Mar 1;1(7905):480-4
46957
Stroke. 1997 Mar;28(3):660-4
9056628
J Neurobiol. 1998 Apr;35(1):29-36
9552164
Neurosurgery. 2001 May;48(5):1006-10; discussion 1010-1
11334266