载脂蛋白 E 上的局部遗传修饰改变了加勒比海西班牙裔的阿尔茨海默病风险。
Local ancestry at APOE modifies Alzheimer's disease risk in Caribbean Hispanics.
机构信息
Division of Medical Genetics, University of Washington, Seattle, WA, USA.
Department of Biostatistics, University of Washington, Seattle, WA, USA.
出版信息
Alzheimers Dement. 2019 Dec;15(12):1524-1532. doi: 10.1016/j.jalz.2019.07.016. Epub 2019 Oct 9.
INTRODUCTION
Although the relationship between APOE and Alzheimer's disease (AD) is well established in populations of European descent, the effects of APOE and ancestry on AD risk in diverse populations is not well understood.
METHODS
Logistic mixed model regression and survival analyses were performed in a sample of 3067 Caribbean Hispanics and 3028 individuals of European descent to assess the effects of APOE genotype, local ancestry, and genome-wide ancestry on AD risk and age at onset.
RESULTS
Among the Caribbean Hispanics, individuals with African-derived ancestry at APOE had 39% lower odds of AD than individuals with European-derived APOE, after adjusting for APOE genotype, age, and genome-wide ancestry. While APOE E2 and E4 effects on AD risk and age at onset were significant in the Caribbean Hispanics, they were substantially attenuated compared with those in European ancestry individuals.
DISCUSSION
These results suggest that additional genetic variation in the APOE region influences AD risk beyond APOE E2/E3/E4.
简介
尽管 APOE 与阿尔茨海默病（AD）之间的关系在欧洲血统人群中已得到充分证实，但 APOE 和血统对不同人群 AD 风险的影响仍不清楚。
方法
在 3067 名加勒比西班牙裔和 3028 名欧洲血统个体中进行了逻辑混合模型回归和生存分析，以评估 APOE 基因型、本地血统和全基因组血统对 AD 风险和发病年龄的影响。
结果
在加勒比西班牙裔中，调整 APOE 基因型、年龄和全基因组血统后，APOE 处具有非洲血统的个体患 AD 的几率比具有欧洲血统的个体低 39%。虽然 APOE E2 和 E4 对 AD 风险和发病年龄的影响在加勒比西班牙裔中具有统计学意义，但与欧洲血统个体相比，其影响明显减弱。
讨论
这些结果表明，APOE 区域的其他遗传变异会影响 AD 风险，而不仅仅是 APOE E2/E3/E4。
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