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Clinical Chemistry 46: 1548-1554, 2000;
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(Clinical Chemistry. 2000;46:1548-1554.)
© 2000 American Association for Clinical Chemistry, Inc.

Articles

Genotypes and Phenotypes for Apolipoprotein E and Alzheimer Disease in the Honolulu-Asia Aging Study

Jan W.P.F. Kardaun1, Lon White2,a, Helaine E. Resnick5, Helen Petrovitch2, Santica M. Marcovina3, Ann M. Saunders4, Dan J. Foley5 and Richard J. Havlik5

1 Archa B.V., 3039 HK Rotterdam, The Netherlands.

2 Kuakini Medical Center and the Pacific Health Research Institute, Honolulu, Hawaii 96813.

3 University of Washington School of Medicine, Northwest Lipid Laboratories, Seattle, WA 98103.

4 Joseph and Kathleen Bryan Alzheimer’s Disease Research Center, Duke University School of Medicine, Durham, NC 27710.

5 National Institute on Aging, Bethesda, MD 20892.
a Address correspondence to this author at: Pacific Health Research Institute, Suite 306, 846 South Hotel St., Honolulu, HI 96813. Fax 808-524-4315; e-mail white{at}hawaii-health.com

Background: The utility of apolipoprotein E (ApoE) type as an indicator of genetic susceptibility to Alzheimer disease (AD) depends on the reliability of typing. Although ApoE protein isoform phenotyping is generally assumed equivalent to genotyping from DNA, phenotype-genotype differences have been reported.

Methods: ApoE genotype and phenotype results were examined for 3564 older (ages 71–93 years) Japanese-American male participants of the Honolulu-Asia Aging Study, an ongoing population-based study of aging and dementia.

Results: Both methods demonstrated similar associations of ApoE type with AD: a direct association with ApoE4 and a less dramatic inverse association ApoE2. Advanced age did not appear to influence the ApoE4-AD association. The association with AD among ApoE4 homozygotes [odds ratio (OR) = 14.7] was higher than expected based on an observed OR of 2.0 in heterozygotes. Phenotype-genotype nonconcordance was more frequent for ApoE2 than for ApoE4. The ApoE2 phenotype occurred at a frequency of 7.9% vs a genotype frequency of 4.9%, corresponding to a probability of 56% that an individual with ApoE2 phenotype had the same genotype.

Conclusions: Whereas E4 and E2 phenotypes and genotypes were comparably associated with AD, neither method would be expected to substantially improve the efficiency of case finding in the context of population screening beyond prediction based on age and education. Nonconcordance of phenotype and genotype was substantial for E2 and modest for E4 in this population. The ApoE4-AD association was independent of age.




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