<i>APOE</i> Genotype and Serum Cholesterol in Predicting Risk for Early Death from Ischemic Stroke in Men and Women

Abstract

Background: We recently discovered that APOE ε3/ε4 genotype in men and APOE ε2/ε3 genotype in women are associated with increased risk of death from ischemic stroke (IS). One of the main physiological roles of apolipoprotein E is participation in cholesterol metabolism. A significant association of low serum cholesterol level with increased risk of death from stroke was documented. So, we aimed to establish if an association exists between APOE genotype, serum cholesterol and 1-month mortality in IS. Methods: We studied 666 patients (330 men, 336 women) with a diagnosis of IS. Total serum cholesterol (TC) was measured with the method of Abbott Spectrum (USA). APOE genotyping was performed by PCR-RFLP method. Results:The highest frequency of low serum TC was associated with APOE ε2/ε3 genotype (both in men and in women). Low serum TC was associated with increased mortality rate only in women; this effect was evident only in females not possessing APOE ε2/ε3. Female patients with APOE ε2/ε3 genotype had high 1-month mortality rate independently from serum TC. In multiple regression analyses APOE ε3/ε4 genotype in men and APOE ε2/ε3 genotype in women predicted risk of death independently from serum TC and also from other potential pre- and post-stroke prognostic factors. Conclusion:APOE ε3/ε4 genotype in men and APOE ε2/ε3 in women are associated with increased 30-day mortality in stroke. This effect seems be independent from serum cholesterol.

The APOE polymorphism and 1-year outcome in ischemic stroke: genotype–gender interaction

“…In one study, no association was observed (20), and in the other, a trend toward survival benefit associated with an APOE ε4 allele (18) was documented. In a previous study we documented a significant, gender‐dependent effect of APOE ε3/ε4 genotype on increased risk of early death after the IS (11). In this study we document a significant, men‐specific, association of the E4 genotype with greater neurological deficit on admission, and with increased risk of death within the period up to 1 year after the IS.…”

“…Two previous reports suggested that the total serum cholesterol is an important factor which determines mortality in stroke (44, 45). However, our previous analysis failed to confirm that lipid influences were responsible for the gender‐dependent differences in APOE genotype effects on 1‐month stroke mortality (11).…”

“…In many studies the unfavorable effect of the apoE4 isoform was detected, compared with the E3 and E2 isoforms (the last one is the less intensively studied). The possession of the APOE ε4 allele was associated with increased risk/greater severity/unfavorable outcome in chronic central nervous system disorders, including neurodegenerative diseases as Alzheimer disease (1), Parkinson disease (2, 3), multiple sclerosis (4), amyotrophic lateral sclerosis (5), as well as in acute brain injuries including intracerebral hemorrhage (6, 7), traumatic brain injury (8–10), and ischemic stroke (IS) (11). Experimental studies supplied an explanation for this phenomenon.…”

“…During recent years still more evidence is accumulated that APOE ε4 effects in human disease may be modulated by age and gender (8, 21–23). In our previous study, we reported on association between the APOE ε3/ε4 genotype and increased 1‐month mortality after the IS in men patients (11). In this study, we evaluated APOE genotypes to gain an evidence for their effects on acute neurological impairment and on stroke outcomes up to 1 year, with taking into consideration possible genotype–age and genotype–gender interactions.…”

Cognitive Function, <b><i>APOE</i></b> Gene Polymorphisms, and Thyroid Status Associations in Postmenopausal Women in Poland

“…The presence of the APOE ε4 allele is associated with oxidative stress, microglia invasion, inflammation and an increased risk of premature atherosclerosis, which can be at least partially responsible for the increased risk of dementia and AD in ε4 allele carriers. Comparing to ApoE ε3, the ApoE ε4 isoform is more susceptible to proteolysis, leading to the accumulation of reactive fragments of ApoE ε4 in the cytosol, which results in cytoskeleton damage and neurodegeneration [8,9]. Teng et al [10] demonstrated that low plasma ApoE levels are significantly correlated with a smaller hippocampal size in patients with normal recognition or cognitive impairment.…”