BACKGROUND: An increased risk of Alzheimer's disease (AD) has been reported in young mothers of Down's syndrome (DS) probands. Allele epsilon4 of the apolipoprotein E (apoE) gene is a genetic susceptibility factor for AD. We examined the distribution of apoE alleles in people with DS and their parents. METHODS: We studied 188 Danish people with non-mosaic free trisomy 21 of known parental origin (determined by DNA polymorphism analysis), and their parents, chosen from a population-based study of DS, and compared the frequency of apoE alleles with a previously published Danish control sample. FINDINGS: In people with DS, there was no significant difference in apoE allele distribution compared with controls. The frequency of allele epsilon4 in the fathers (11.8%) was significantly lower than in controls (17.4%, p=0.02). The frequency of allele epsilon4 in the mothers (19.4%) was not significantly different from that of controls. Nevertheless, in young mothers with a meiosis II error, epsilon4 frequency was 30.0%, significantly higher than in older mothers with a meiosis II error (13.0%, p=0.03). INTERPRETATION: We suggest that apoE allele epsilon4 is a risk factor for meiosis II non-disjunction in young mothers, but the biological role of apoE in oocytes remains to be investigated.
BACKGROUND: An increased risk of Alzheimer's disease (AD) has been reported in young mothers of Down's syndrome (DS) probands. Allele epsilon4 of the apolipoprotein E (apoE) gene is a genetic susceptibility factor for AD. We examined the distribution of apoE alleles in people with DS and their parents. METHODS: We studied 188 Danish people with non-mosaic free trisomy 21 of known parental origin (determined by DNA polymorphism analysis), and their parents, chosen from a population-based study of DS, and compared the frequency of apoE alleles with a previously published Danish control sample. FINDINGS: In people with DS, there was no significant difference in apoE allele distribution compared with controls. The frequency of allele epsilon4 in the fathers (11.8%) was significantly lower than in controls (17.4%, p=0.02). The frequency of allele epsilon4 in the mothers (19.4%) was not significantly different from that of controls. Nevertheless, in young mothers with a meiosis II error, epsilon4 frequency was 30.0%, significantly higher than in older mothers with a meiosis II error (13.0%, p=0.03). INTERPRETATION: We suggest that apoE allele epsilon4 is a risk factor for meiosis II non-disjunction in young mothers, but the biological role of apoE in oocytes remains to be investigated.
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