Apolipoprotein E and Alzheimer's disease: ethnic variation in genotypic risks.
The presence of the apolipoprotein epsilon 4 (apo epsilon 4) allele significantly increases the risk of Alzheimer's disease. Whether this is due to biological effects of the apo epsilon 4 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 epsilon 4. Overall, the risk between Alzheimer's disease and apo epsilon 4 heterozygosity was also increased by twofold, but the association was somewhat weaker for African-Americans than for Hispanics and whites. In contrast, the apo epsilon 2/epsilon 3 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 apo epsilon *4 was significantly higher in patients than control subjects in all ethnic groups at age 70 or younger, reflecting the higher proportion of apo epsilon 4 homozygotes, but this difference diminished with increasing age. The allelic frequency of apo epsilon *2 for African-Americans and Hispanics, but not whites, was significantly higher in patients than control subjects, but only after age 70.(ABSTRACT TRUNCATED AT 250 WORDS)
Maestre
G
G
Center for Alzheimer's Disease Research, New York, NY.
Ottman
R
R
Stern
Y
Y
Gurland
B
B
Chun
M
M
Tang
M X
MX
Shelanski
M
M
Tycko
B
B
Mayeux
R
R
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000208:ethnology* / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics*; D044383:Black People / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D044465:White People / Q000235:genetics; D001741:Black or African American
D001057:Apolipoproteins E