Abstract
ObjectiveThis study considers the use of a rapid molecular assay to evaluate apolipoprotein E (ApoE) status in military subjects who have been exposed to high altitude. We hypothesize that ApoE status may be protective against developing brain white matter hyperintensities (WMHs) after high altitude exposure.ResultsWe tested 92 subjects who had been exposed to altitudes above 25,000 ft mean sea level, either as pilots or as altitude chamber technicians. We determined subject genetic status using rapid Taqman-style polymerase chain reaction genotyping and evaluated the association of ApoE subtype versus brain lesions using t-tests and two-way analyses of variance. Our results indicate that there is no significant association between ApoE genotype status and the presence of WMHs after high altitude exposure. We did observe a significantly higher number of hours spent at altitude for subjects with the ApoE E2 allele; however, the mechanism by which this may occur is not determined in this study. To more fully elucidate this effect, larger populations would be required to observe greater numbers of subjects with the E2 and E4 alleles.
Highlights
Genetic variants of the apolipoprotein E (ApoE) gene have been associated with several neurodegenerative disorders including Alzheimer’s disease, cognitive impairment, and multiple sclerosis, as well as with varying rates of recovery from traumatic brain injury [1–3]
In a meta-analysis of 42 published studies conducted by Schilling et al the ApoE4 and ApoE2 genes were associated with increasing burden in magnetic resonance imaging (MRI) markers for both hemorrhagic and ischemic cerebrovascular disease, while ApoE2 correlated with increasing brain white matter hyperintensities (WMHs) [7]
In previous studies from our group [8, 9], increased WMH burden was associated with repetitive nonhypoxic hypobaric exposure, neurologic decompression sickness, and lower neurocognitive test performance as measured on computer-based neurocognitive tests
Summary
Overall ApoE allele frequencies were consistent with the global allele distribution [12]: ApoE2 = 7.6%, ApoE3 = 78.8%, and ApoE4 = 13.5% These alleles were spread across four genotypes: ApoE2/ApoE3, ApoE3/ ApoE3, ApoE3/ApoE4, and ApoE4/ApoE4. Performing a two-way analysis of variance revealed that the ApoE genotype status accounted for 0.21% of the total variance in the population, the interaction between genotype and collected phenotypes accounted for 1.99%, and the differences in the phenotypes themselves accounted for 16.92% of the variance. The effects of both the interaction and the genotype are not considered significant. The range of times for the entire population was from 9 to 2000 h
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