APOLIPOPROTEIN-E AND ALZHEIMER-DISEASE - GENOTYPE-SPECIFIC RISKS BY AGE AND SEX

The distribution of apolipoprotein E (APOE) genotypes as a function of age and sex has been examined in a French population of 417 Alzheimer disease (AD) patients and 1,030 control subjects. When compared to th e APOE epsilon 3 allele, an increased risk associated with the APOE ep silon 4 allele (odds ratio [OR] [epsilon 4] = 2.7 with 95% confidence interval [CI] = 2.0-3.6; P < .001) and a protective effect of the APOE epsilon 2 allele (OR[epsilon 2] = 0.5 with 95% CI = 0.3-0.98; P = .01 2) were retrieved. An effect of the epsilon 4 allele dosage on suscept ibility was confirmed (OR[epsilon 4/epsilon 4] vs. the epsilon 3/epsil on 3 genotype = 11.2 [95% CI = 4.0-31.6]; OR[epsilon 3/epsilon 4] vs. the epsilon 3/epsilon 3 genotype = 2.2 [95% CI = 1.5-3.5]). The freque ncy of the epsilon 4 allele was lower in male cases than in female cas es, but, since a similar difference was found in controls, this does n ot lead to a difference in OR between sex. ORs for the epsilon 4 allel e versus the epsilon 3 allele, OR(epsilon 4), were not equal in all ag e classes: OR(epsilon 4) in the extreme groups with onset at <60 years or >79 years were significantly lower than those from the age groups 60-79 years. In epsilon 3/epsilon 4 individuals, sex-specific lifetime risk estimates by age 85 years (i.e., sex-specific penetrances by age 85 years) were 0.14 (95% CI 0.04-0.30) for men and 0.17 (95% CI 0.09- 0.28) for women.