Interaction of the apolipoprotein E and CI loci in predisposing to late-onset Alzheimer's disease.

OBJECTIVE

The association between Alzheimer's disease (AD) and alleles at the ApoE and the ApoCI loci were tested.

BACKGROUND

The ApoE alleles, in linkage disequlibrium with ApoCI alleles, have been reported as associated with (epsilon4) or protective for (epsilon2) AD.

METHODS

The patients comprise two samples, with a total of 176 whose diagnosis has been confirmed as having probable AD and 226 controls. Genomic DNA was extracted from blood or transformed lymphocytes. Logistic regression was used to determine the effects of alleles at the ApoE and ApoCI loci after allowing for the effects of age and gender.

RESULTS

The effects of the ApoE epsilon2, epsilon3, and epsilon4 alleles were individually studied first; ignoring the ApoCI locus, only the dominant or additive effect of epsilon4 is significant after considering age, gender, and sample--the dominant effect being slightly more significant. The effect of epsilon4 (when only the ApoE locus is included in the model) was larger than recently reported: the odds ratio was 5.57 (95% CI, 3.46 to 8.98). Similarly, when the ApoCI locus was examined, ignoring the ApoE locus, a dominant effect of A was found to be slightly more significant than an additive effect. Finally, models were considered that included the dominant effect of epsilon4, the dominant effect of A, and their interaction. A model that included only the interaction of ApoE and ApoCI yielded the largest odds ratio, 5.89 (95% CI, 3.64 to 9.53).

CONCLUSIONS

Association of AD with both the ApoE epsilon4 and ApoCI A alleles was found. The increased risk of AD among carriers of epsilon4 was found to be higher among those who also bear the ApoCI A allele but this may be due to a dose effect of the epsilon4 allele.