6.16.2008

APOEe4 Genetic Marker is an HIV Severity Accelerator
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Gladstone Institute at UCSF and University of Texas researchers have found the APOEe4 genetic marker, known as the most significant genetic risk determinant of Alzheimer's Disease and a factor in heart disease and stroke, also may play a role in the severity of HIV in people who have the disease. Results were published in the Proceedings of the National Academy of Sciences.

A seemingly trifling sequence difference of just one amino acid has profound implications for the structure and function of the APoE4 protein. ApoE4 has an extra intra-molecular bond that results in a more compact structure, and it also is more likely to be unstable, linked to its deleterious effects. Although the apoE3 gene is the most prevalent in all human populations, with frequencies of 50%, the genetic variant that leads to production of apoE4 is also widely distributed; its prevalence is 15.% (Some sources estimate at 20% or more of all humans)

Those with two copies of APOEe4, the homogeneous zygote, had a much more rapid progressions of HIV, leading to death, than those with two copies APOEe3.

The APOEe4 protein is smaller and more compact, but more unstable - than the APOEe2 and APOEe3. The reason for the APOEe4 mutation, it is hypothesized, helped people metabolize a lean, scarce diet and avoid starvation and possibly lowered the chance of child mortality. It also may be linked to colder temperatures, or possibly to those groups with the mutation who migrated into northern latitudes - it is more prevalent in Finland as a percentage of the population than anywhere else on earth, and also amongst relatively homogeneous ethnic groups (for example, German Russians) where increased APOEe4 risk has followed such groups even after migrating to North America where it is seen in distinct family histories of Alzheimer's Disease.

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