http://repub.eur.nl/res/aut/11247/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/5973/ 2002-12-01T00:00:00Z Age-related maculopathy (ARM) is a multifactorial disorder known to have a substantial genetic component. The epsilon4 allele of the apolipoprotein E gene (APOE-4) has previously been reported to have a protective effect on ARM risk, while the APOE-2 allele may increase disease risk. This study combined four independent data sets (three US and one European) of Caucasian ARM patients and controls in order to obtain better statistical power to examine the role of APOE in ARM. APOE genotype and allele frequencies were compared for 617 ARM cases and 1260 controls, adjusting for age and sex differences between the two groups via multiple logistic regression. The protective effect of the APOE-4 allele on ARM risk was confirmed (age- and sex-adjusted odds ratio (OR) for APOE-4 carriers 0.54, 95% confidence interval (CI) 0.41-0.70, p < 0.0001). The effect of APOE-4 did not differ significantly between males and females and was observed consistently for both atrophic and neovascular ARM. Evidence for an increased risk of ARM due to the APOE-2 allele was found for men, but not for women (OR for men 1.54, 95% CI 0.97-2.45; OR for women 0.74, 95% CI 0.52-1.06, p = 0.01 for interaction of sex and APOE-2 carrier status). These data confirm that the APOE-4 allele, or an allele in linkage disequilibrium with it, reduces the risk of ARM. They also suggest that the effect of the APOE-2 allele may vary by gender, and that APOE-2 may confer an increased risk only to males. http://repub.eur.nl/res/pub/9477/ 2000-01-01T00:00:00Z 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.