Apolipoprotein E and alzheimer's disease: Ethnic variation in genotypic risks

The presence of the apolipoprotein ε4 (apo ε4) allele significantly increases the risk of Alzheimer's disease. Whether this is due to biological effects of the apo ε4 protein or reflects linkage disequilibrium with an as yet unidentified Alzheimer's disease susceptibility gene is of critical importance. In a community study in northern Manhattan we found a fivefold increase in the risk of Alzheimer's disease among African‐Americans, Hispanics, and whites homozygous for apo ε4. Overall, the risk between Alzheimer's disease and apo ε4 heterozygosity was also increased by twofold, but the association was somewhat weaker for African‐Americans than for Hispanics and whites. In contrast, the apo ε2/ε3 genotype was associated with an eightfold increased risk of Alzheimer's disease in African‐Americans but it was associated with reduced risk in whites. Variability in the strength and type of association between Alzheimer's disease and the apo E polymorphisms in the three ethnic groups could not be fully explained by age differences. The allelic frequency of apoε*4 was significantly higher in patients than control subjects in all ethnic groups at age 70 or younger, reflecting the higher proportion of apo ε4 homozygotes, but this difference diminished with increasing age. The allelic frequency of apoε*2 for African‐Americans and Hispanics, but not whites, was significantly higher in patients than control subjects, but only after age 70. Though these findings need confirmation, they suggest that modifier genes or environmental factors may interact selectively with apo ε4 in African‐Americans to weaken the association with Alzheimer's disease or that the apo E allelic system is in linkage disequilibrium with a nearby, as yet unidentified Alzheimer's disease susceptibility locus.

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