The Influence of Apolipoprotein E Genotype on Outcome after Spontaneous Subarachnoid Hemorrhage: A Preliminary Study.
Dunn, Laurence T. Ph.D.; Stewart, Elaine R.G.N.; Murray, Gordon D. Ph.D.; Nicoll, James A.R. M.D.; Teasdale, Graham M. F.Med.Sci.
48(5):1006-1011, May 2001.
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OBJECTIVE: Possession of an apolipoprotein E (APOE)[epsilon]4 allele has been shown to be associated with a poor outcome after closed head injury and spontaneous intracerebral hemorrhage but not after ischemic stroke. This study assessed the influence of the APOE genotype on outcome in patients admitted to a neurosurgical unit with spontaneous subarachnoid hemorrhage.
METHODS: A total of 100 patients with spontaneous subarachnoid hemorrhage were studied. Four patients were excluded because the diagnosis of subarachnoid hemorrhage was not confirmed. The incidence of rehemorrhage and delayed ischemia and the outcome at 6 months were determined using the Glasgow Outcome Scale. APOE genotypes were determined by polymerase chain reaction and restriction enzyme digestion.
RESULTS: Allele frequencies in this patient group were 0.04 for [epsilon]2, 0.86 for [epsilon]3, and 0.1 for [epsilon]4. Of 96 patients, 72 had an aneurysmal hemorrhage and 1 had a hemorrhage from an arteriovenous malformation. In 14 patients, the results of angiography were negative, and in 9, no angiogram was performed. Of the 96 patients, 20 had one or more [epsilon]4 allele. Outcome at 6 months was no worse in patients with one or more [epsilon]4 allele than in those with no [epsilon]4 allele (odds ratio, 0.98; 95% confidence interval, 0.35-2.74). None of the 12 patients who experienced delayed ischemic deterioration had an [epsilon]4 allele. Of the 20 patients with an [epsilon]4 allele, 3 had a rehemorrhage, as compared with 6 of 76 patients without an [epsilon]4 allele.
CONCLUSION: There was underrepresentation of the [epsilon]4 allele in this group when compared with previously studied cases of subarachnoid hemorrhage with a fatal outcome and with the general population. This suggests that patients with the [epsilon]4 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 [epsilon]4 allele and poor outcome in patients admitted to a neurosurgical unit with spontaneous subarachnoid hemorrhage, although the wide confidence interval does not preclude a clinically relevant association between APOE genotype and outcome. The findings indicate that an association between genotype and the development of delayed ischemic complications after subarachnoid hemorrhage may be possible.
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