Apolipoprotein E promoter genotypes are not associated with white matter hyperintensity development in high-altitude careers

This study sought to determine if there is an association between variants in the apolipoprotein E (ApoE) promoter regions and development of white matter hyperintensities (WMH) in military subjects who have been exposed to high altitude. In an earlier study, we found that ApoE status did not correlate with WMH development, and here we hypothesized that regulation of APOE protein expression may be protective. Our cohort of 92 subjects encountered altitude exposures above 25,000 feet mean sea level through their occupations as pilots or altitude chamber technicians. Using Taqman-style polymerase chain reaction genotyping and t-tests and two-way analyses of variance we found no significant association between ApoE promoter genotypes and the presence, volume, or quantity of WMHs after high altitude exposure. Taken together, the observations that neither ApoE genotype status nor promoter status are associated with WMH properties, we believe that the mechanism of action for developing WMH does not derive from ApoE, nor would therapies for ApoE-mediated neurodegeneration likely benefit high altitude operators.