Hendrie Hugh C, Murrell Jill, Baiyewu Olusegun, Lane Kathleen A, Purnell Christianna, Ogunniyi Adesola, Unverzagt Frederick W, Hall Kathleen, Callahan Christopher M, Saykin Andrew J, Gureje Oye, Hake Ann, Foroud Tatiana, Gao Sujuan
Indiana University Center for Aging Research, Indianapolis, Indiana, USA.
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Int Psychogeriatr. 2014 Jun;26(6):977-85. doi: 10.1017/S1041610214000167. Epub 2014 Feb 24.
There is little information on the association of the APOEe4 allele and AD risk in African populations. In previous analyses from the Indianapolis-Ibadan dementia project, we have reported that APOE ε4 increased the risk for Alzheimer's disease (AD) in African Americans but not in Yoruba. This study represents a replication of this earlier work using enriched cohorts and extending the analysis to include cognitive decline.
In this longitudinal study of two community dwelling cohorts of elderly Yoruba and African Americans, APOE genotyping was conducted from blood samples taken on or before 2001 (1,871 African Americans & 2,200 Yoruba). Mean follow up time was 8.5 years for African Americans and 8.8 years for Yoruba. The effects of heterozygosity or homozygosity of ε4 and of the possession of e4 on time to incident AD and on cognitive decline were determined using Cox's proportional hazards regression and mixed effects models.
After adjusting for covariates, one or two copies of the APOE ε4 allele were significant risk factors for incident AD (p < 0.0001) and cognitive decline in the African-American population (p < 0001). In the Yoruba, only homozygosity for APOE ε4 was a significant risk factor for AD (p = 0.0002) but not for cognitive decline (p = 0.2346), however, possession of an e4 allele was significant for both incident AD (p = 0.0489) and cognitive decline (p = 0.0425).
In this large longitudinal comparative study, APOE ε4 had a significant, but weaker, effect on incident AD and on cognitive decline in Yoruba than in African Americans. The reasons for these differences remain unclear.
关于非洲人群中APOEε4等位基因与阿尔茨海默病（AD）风险之间的关联，相关信息较少。在印第安纳波利斯 - 伊巴丹痴呆项目之前的分析中，我们报告称APOEε4增加了非裔美国人患阿尔茨海默病（AD）的风险，但在约鲁巴人中并非如此。本研究使用富集队列重复了这项早期工作，并将分析扩展至包括认知衰退。
在这项针对约鲁巴和非裔美国老年人的两个社区居住队列的纵向研究中，对2001年或之前采集的血样进行APOE基因分型（1871名非裔美国人及2200名约鲁巴人）。非裔美国人的平均随访时间为8.5年，约鲁巴人为8.8年。使用Cox比例风险回归和混合效应模型确定ε4的杂合性或纯合性以及携带ε4对AD发病时间和认知衰退的影响。
在调整协变量后，APOEε4等位基因的一份或两份拷贝是非裔美国人群中AD发病（p < 0.0001）和认知衰退（p < 0.0001）的显著风险因素。在约鲁巴人中，仅APOEε4纯合性是AD的显著风险因素（p = 0.0002），但不是认知衰退的风险因素（p = 0.2346），然而，携带ε4等位基因对AD发病（p = 0.0489）和认知衰退（p = 0.0425）均具有显著意义。
在这项大型纵向比较研究中，APOEε4对约鲁巴人AD发病和认知衰退的影响显著，但比对非裔美国人的影响弱。这些差异的原因尚不清楚。
