Significant effect of APOE Epsilon 4 Genotype on the risk of dementia in Alzheimer's disease and mortality in persons with Down Syndrome
Significant effect of APOE Epsilon 4 Genotype on the risk of dementia in Alzheimer's disease and mortality in persons with Down Syndrome
复制标题
DOI：
10.1002/gps.2039
复制
发表时间：
2008-11-01
影响因子：
4
通讯作者：
Zigman, W. B.
中科院分区：
文献类型：
--
作者：
Prasher, V. P.;Sajith, S. G.;Zigman, W. B.
目的几乎所有的唐氏综合征(DS)患者都有阿尔茨海默病(DAD)痴呆的神经病理表现，但并不是所有的患者都有临床精神病理改变。目的探讨载脂蛋白(ApoE)基因等位基因变异在DS患者DAD发生发展及病死率中的作用。方法对受试者进行2~14次序贯评估，平均随访6年。根据制订智障人士痴呆症诊断标准工作组的建议，确认了痴呆症状态。结果252名个体获得了APOE基因分型结果。与携带epsilon 3等位基因的患者相比，携带apoE epsilon 4等位基因的患者发生DAD的风险显著增加(HR=1.80，95%CI：1.12-2.79)，DAD发病早(55.0vs57.0岁；p=0.0027)，死亡进展更快(分别为4.2年vs.5.4年，p=0.048)。在非痴呆的DS患者中，epsilon 4等位基因与早17年死亡相关(平均生存年龄，55.7岁比72.7岁；HR=5.9，95%CI：1.7~21.3)。结论本研究强调了APOE基因与DS患者发病率和死亡率的关系，具有重要的临床意义。我们建议在DS患者中进行APOE基因筛查，以确定那些有DAD和过早死亡风险的人。携带A等位基因的非痴呆DS患者早期死亡的潜在原因尚需进一步研究。版权所有(C)2008 John Wiley&Sons，Ltd.
Objective Virtually all adults with Down syndrome (DS) have neuropathological manifestations of Dementia in Alzheimer's disease (DAD) but not all develop clinical psychopathology. The effect of allelic variants of Apolipoprotein (APOE) gene in development and progression of DAD and mortality in persons with DS is examined.Methods Recruited participants with DS underwent two to 14 sequential assessments over a follow up period of 6 years on average and their APOE genotype determined. Dementia status was confirmed as recommended by the Working Group for the Establishment of Criteria for the Diagnosis of Dementia in Individuals with Intellectual Disability. Results APOE genotype results were available for 252 individuals. Participants with APOE epsilon 4 allele had significantly higher risk of developing DAD (HR = 1.8, 95% CI: 1.12-2.79), had an earlier onset of DAD (55.0 vs 57.0 years; p = 0.0027) and a more rapid progression to death compared with participants with epsilon 3 allele (4.2 years vs. 5.4 years, respectively, p = 0.048). In non-demented persons with DS, epsilon 4 allele was associated with earlier death by 17 years (mean survival age, 55.7 vs. 72.7 years; HR = 5.9, 95% CI: 1.7-21.3).Conclusions This study highlights the relationship of APOE genotype to morbidity and mortality in persons with DS which has important clinical implications. We recommend screening for APOE genotype in persons with DS to identify those at risk of DAD and premature death. Further research is required to investigate the underlying reasons for the early mortality in non-demented DS persons with an A allele. Copyright (C) 2008 John Wiley & Sons, Ltd.