Articles: apolipoproteins-e.
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Possession of an apolipoprotein E (APOE)epsilon4 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. ⋯ There was underrepresentation of the epsilon4 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 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 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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Variation in the outcome after aneurysmal subarachnoid hemorrhage (SAH) is not fully explained by known prognostic factors. APOE genotype is the most important genetic determinant of susceptibility to Alzheimer's disease, and it is also shown to be associated with the outcome after traumatic brain injury. We studied the association of apolipoprotein E polymorphism with the outcome after aneurysmal SAH. ⋯ Our findings show a significant genetic association of APOE polymorphism with outcome after spontaneous aneurysmal SAH. Genetic factors thus seem to explain a part of individual differences in the recovery of SAH.
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Anesthesia and analgesia · Apr 2001
Clinical TrialApolipoprotein E polymorphisms and age at first coronary artery bypass graft.
Apolipoprotein E (apoE) polymorphisms are heritable determinants of total and low-density lipoprotein cholesterol. The impact of apoE4 genotypes on the severity of atherosclerosis has been debated; however, recent studies have identified a correlation between apoE4 genotype and atherosclerosis. We assessed the impact of apoE4 genotype on age at first coronary artery bypass graft (CABG), hypothesizing that patients with the apoE4 allele are predisposed to coronary artery disease and present earlier for coronary revascularization. We assessed individual apoE genotypes and age in 560 patients undergoing primary CABG, by using analysis of variance (ANOVA) and controlling for gender. Because of the small number of patients in individual genotype groups, we compared patients with one or more copies of the apoE4 allele with those having no copies of the allele, again controlling for gender. A comparison of patients with one or more copies of the apoE4 allele with patients without the allele showed an earlier age at first CABG for those with the allele (P: = 0.032). Gene-dose analysis was also significant (P: = 0.012); patients with two copies of the allele presented at 54.2 +/- 6.9 yr. We report that the apoE4 allele is linked to age at first CABG. Identifying at-risk individuals may help prevent atherosclerosis. Further study is needed to define the mechanism of this association, and to define which coronary intervention is appropriate, based on long-term outcome. ⋯ A correlation exists between apolipoprotein E (apoE) genotypes and the severity of atherosclerosis. We hypothesized that patients with the apoE4 allele are predisposed to coronary artery disease and present earlier for coronary artery bypass graft (CABG). Individuals with the apoE4 allele presented earlier for CABG, and the apoE4 allele is linked to age at first CABG.
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Recently, Tardiff and colleagues have suggested that the presence of the apolipoprotein E, epsilon4 allele was associated with increased likelihood of cognitive decline after coronary artery bypass grafting. The objective of the current study was to replicate this earlier work using an increased sample size. The increased sample also enabled an analysis by individual genotype in cognitive decline after coronary artery bypass grafting. ⋯ This study suggests that the epsilon4 allele is not associated with cognitive decline in the weeks after coronary artery bypass grafting.
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Alzheimer's disease (AD) is the most common cause of progressive decline of cognitive function in aged humans, and is characterized by the presence of numerous senile plaques and neurofibrillary tangles accompanied by neuronal loss. Some, but not all, of the neuropathological alterations and cognitive impairment in AD can be reproduced genetically and pharmacologically in animals. It should be possible to discover novel drugs that slow the progress or alleviate the clinical symptoms of AD by using these animal models. We review the recent progress in the development of animal models of AD and discuss how to use these model animals to evaluate novel anti-dementia drugs.