Avramopoulos D, Mikkelsen M, Vassilopoulos D, Grigoriadou M, Petersen M B
Department of Genetics, Institute of Child Health, Athens, Greece.
Lancet. 1996 Mar 30;347(9005):862-5. doi: 10.1016/s0140-6736(96)91346-x.
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.
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.
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).
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.
据报道，唐氏综合征（DS）先证者的年轻母亲患阿尔茨海默病（AD）的风险增加。载脂蛋白E（apoE）基因的ε4等位基因是AD的遗传易感性因素。我们研究了DS患者及其父母中apoE等位基因的分布情况。
我们研究了188名丹麦非嵌合型游离21三体患者（其亲代来源已知，通过DNA多态性分析确定）及其父母，这些患者选自一项基于人群的DS研究，并将apoE等位基因频率与先前发表的丹麦对照样本进行比较。
与对照组相比，DS患者的apoE等位基因分布无显著差异。父亲中ε4等位基因的频率（11.8%）显著低于对照组（17.4%，p=0.02）。母亲中ε4等位基因的频率（19.4%）与对照组无显著差异。然而，在减数分裂II错误的年轻母亲中，ε4频率为30.0%，显著高于减数分裂II错误的年长母亲（13.0%，p=0.03）。
我们认为apoE等位基因ε4是年轻母亲减数分裂II不分离的危险因素，但apoE在卵母细胞中的生物学作用仍有待研究。
