APOLIPOPROTEIN-E ALLELE DISTRIBUTION IN PARENTS OF DOWNS-SYNDROME CHILDREN

Background An increased risk of Alzheimer's disease (AD) has been repo rted in young mothers of Down's syndrome (DS) probands. Allele epsilon 4 of the apolipoprotein E (apoE) gene is a genetic susceptibility fac tor for AD. We examined the distribution of apoE alleles in people wit h DS and their parents. Methods We studied 188 Danish people with non- mosaic, free trisomy 21 of known parental origin (determined by DNA po lymorphism analysis), and their parents, chosen from a population-base d study of DS, and compared the frequency of apoE alleles with a previ ously published Danish control sample. Findings In people with DS, the re was no significant difference in apoE allele distribution compared with controls. The frequency of allele epsilon 4 in the fathers (11.8% ) was significantly lower than in controls (17.4%, p=0.02). The freque ncy of allele epsilon 4 in the mothers (19.4%) was not significantly d ifferent from that of controls. Nevertheless, in young mothers with a meiosis II error, epsilon 4 frequency was 30.0%, significantly higher than in older mothers with a meiosis II error (13 0%, p=0.03). Interpr etation We suggest that apoE allele epsilon 4 is a risk factor for mei osis II non-disjunction in young mothers, but the biological role of a poE in oocytes remains to be investigated.