Allele ɛ4 of APOE is a stronger predictor of Alzheimer risk in Sicily than in continental South Italy

The genotype of apolipoprotein E was examined in 173 sporadic Alzheimer's disease (AD) patients, 132 with late onset (LOAD) and 41 with early onset (EOAD), and in 174 healthy matched controls from Sicily. Despite a low frequency of the ɛ4 allele (6.3%, 95% CI: 4.2-9.4) in controls, ɛ4 allele was a stronger predictor of AD risk (odds ratio: 5.8, 95% CI: 3.5-9.4; p < 0.0001) than in most of the studies performed in other regions of Italy, and it has no influence on age at onset. ɛ4/ɛ4 and ɛ4/ɛ3 genotypes were similar predictors of AD risk. Conversely, a decreased risk was found in ɛ3 allele carriers (odds ratio: 0.3, 95% CI: 0.2-0.4; p < 0.0001), which remained significant when considering EOAD cases only (odds ratio: 0.2, 95% CI: 0.1-0.4, p < 0.0001). In conclusion, differences in association strength of ɛ4 allele with AD between Sicily and other regions of Italy suggest an influence of complex gene-gene and gene-environment interactions.