Lt. Dunn et al., The influence of apolipoprotein E genotype on outcome after spontaneous subarachnoid hemorrhage: A preliminary study, NEUROSURGER, 48(5), 2001, pp. 1006-1010
OBJECTIVE: Possession of an apolipoprotein E (APOE)epsilon4 allele has been
shown to be associated with a poor outcome after closed head injury and sp
ontaneous intracerebral hemorrhage but not after ischemic stroke. This stud
y assessed the influence of the APOE genotype on outcome in patients admitt
ed to a neurosurgical unit with spontaneous subarachnoid hemorrhage.
METHODS: A total of 100 patients with spontaneous subarachnoid hemorrhage w
ere studied. Four patients were excluded because the diagnosis of subarachn
oid hemorrhage was not confirmed. The incidence of rehemorrhage and delayed
ischemia and the outcome at 6 months were determined using the Glasgow Out
come Scale. APOE genotypes were determined by polymerase chain reaction and
restriction enzyme digestion.
RESULTS: Allele frequencies in this patient group were 0.04 for epsilon2, 0
.86 for epsilon3, and 0.1 for epsilon4. Of 96 patients, 72 had an aneurysma
l hemorrhage and 1 had a hemorrhage from an arteriovenous malformation. In
14 patients, the results of angiography were negative, and in 9, no angiogr
am was performed. Of the 96 patients, 20 had one or more epsilon4 allele. O
utcome at 6 months was no worse in patients with one or more epsilon4 allel
e than in those with no epsilon4 allele (odds ratio, 0.98; 95% confidence i
nterval, 0.35-2.74). None of the 12 patients who experienced delayed ischem
ic deterioration had an epsilon4 allele. Of the 20 patients with an epsilon
4 allele, 3 had a rehemorrhage, as compared with 6 of 76 patients without a
n epsilon4 allele.
CONCLUSION: There was underrepresentation of the epsilon4 allele in this gr
oup when compared with previously studied cases of subarachnoid hemorrhage
with a fatal outcome and with the general population. This suggests that pa
tients with the epsilon4 allele who have a subarachnoid hemorrhage are less
likely to be admitted to a neurosurgical unit. This study does not support
an association between possession of an epsilon4 allele and poor outcome i
n patients admitted to a neurosurgical unit with spontaneous subarachnoid h
emorrhage, although the wide confidence interval does not preclude a clinic
ally relevant association between APOE genotype and outcome. The findings i
ndicate that an association between genotype and the development of delayed
ischemic complications after subarachnoid hemorrhage may be possible.