Sawyer Kathryn, Sachs-Ericsson Natalie, Preacher Kristopher J, Blazer Dan G
Department of Psychology, Florida State University, Tallahassee, FL 32306-1270, USA.
Gerontology. 2009;55(1):32-40. doi: 10.1159/000137666. Epub 2008 Jun 5.
Most, but not all, past studies have suggested that the APOE genotype is a risk factor for dementia in whites but not African Americans. This paper first describes explanations as to why some studies may have failed to detect the effect of APOE genotype in African American samples. Briefly, studies have been limited by various methodological problems including small sample sizes, dichotomous measures of cognitive functioning (which tend to be less sensitive to change), and racial bias in assessing demented status.
This paper suggests methods for increasing the likelihood that genuine racial differences will be identified when examining genetic risk factors. Further, we test our model of racial differences in the relationship of APOE genotype and cognitive decline (CD) in a large prospective community sample.
Building on the work of Fillenbaum and colleagues [J Am Geriatr Soc 2001;49:1148-1155], we used data from the Duke EPESE study collected in four waves over a 10-year period (n = 2,076) to illustrate methods which may better assess racial differences in the influence of the APOE epsilon 4 allele on CD. We used multilevel models for repeated measures to examine racial differences in participants' increase in errors on a continuous measure of cognitive functioning as they aged.
We found the APOE epsilon 4 allele to predict CD for both African Americans and whites. Having at least one epsilon 4 allele predicted more cognitive errors at wave 1 and a faster rate of decline for both African Americans and whites over time. While African Americans experienced a faster rate of CD than whites, there was no additional increase in CD from being both African American and a carrier of the epsilon 4 allele.
The study points to several common methodological issues that arise when examining racial differences in genetic influences on health-related outcomes. Further, the study's results highlight the importance of including both African Americans and Caucasians in research concerning the contribution of APOE genotype to CD.
过去大多数（但并非所有）研究表明，APOE基因分型是白人患痴呆症的一个风险因素，而对非裔美国人则不然。本文首先阐述了为何一些研究可能未能在非裔美国人样本中检测到APOE基因分型的影响。简而言之，研究受到各种方法学问题的限制，包括样本量小、认知功能的二分法测量（往往对变化不太敏感）以及评估痴呆状态时的种族偏见。
本文提出了一些方法，以增加在研究遗传风险因素时识别真正种族差异的可能性。此外，我们在一个大型前瞻性社区样本中检验了我们关于APOE基因分型与认知衰退（CD）关系的种族差异模型。
基于Fillenbaum及其同事的研究成果[《美国老年医学会杂志》2001年；49:1148 - 1155]，我们使用了杜克流行病学老年人研究（Duke EPESE）在10年期间分四波收集的数据（n = 2,076），以说明哪些方法可能更好地评估APOE ε4等位基因对CD影响的种族差异。我们使用重复测量的多级模型来检验随着年龄增长，参与者在认知功能连续测量中错误增加方面的种族差异。
我们发现APOE ε4等位基因对非裔美国人和白人的CD都有预测作用。至少有一个ε4等位基因在第一波时预测出更多认知错误，并且随着时间推移，非裔美国人和白人的衰退速度都更快。虽然非裔美国人的CD速度比白人快，但作为非裔美国人且是ε4等位基因携带者并不会使CD进一步增加。
该研究指出了在研究遗传因素对健康相关结果影响的种族差异时出现的几个常见方法学问题。此外，该研究结果强调了在关于APOE基因分型对CD影响的研究中纳入非裔美国人和白种人的重要性。
