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)
Center for Alzheimer's Disease Research, New York, NY.
G
G
Maestre
R
R
Ottman
Y
Y
Stern
B
B
Gurland
M
M
Chun
M X
MX
Tang
M
M
Shelanski
B
B
Tycko
R
R
Mayeux
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