Allelic expression of APOE in human brain:: effects of epsilon status and promoter haplotypes
Allelic expression of APOE in human brain:: effects of epsilon status and promoter haplotypes
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DOI：
10.1093/hmg/ddh299
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发表时间：
2004-11-15
影响因子：
3.5
通讯作者：
O'Donovan, MC
中科院分区：
文献类型：
--
作者：
Bray, NJ;Jehu, L;O'Donovan, MC
APOE 的 epsilon4 单倍型是迟发性阿尔茨海默病 (LOAD) 唯一无可争议的遗传风险因素。有人提出，APOE 基因启动子中的至少两个多态性（-219G>T 和 -491A>T）也可能导致疾病易感性，并通过改变 ApoE 蛋白的表达来调节其结构变化的影响。为了评估顺式作用对人脑中 APOE 表达的影响程度，对来自 epsilon 等位基因杂合个体的皮质 RNA 进行了高度定量的等位基因区分测量。相对于 epsilon3 和 epsilon2 等位基因，观察到 epsilon4 等位基因的表达有小幅但显着的增加（PT 启动子多态性显示包含 -219T 等位基因的单倍型的相对表达显着较低（P=0.02）。我们的数据表明，在人脑中，APOE 表达中的大部分顺式作用变异是由 epsilon4 单倍型造成的，但还有其他小的、与启动子基因型相关的顺式作用影响。
The epsilon4 haplotype of APOE is the only undisputed genetic risk factor for late-onset Alzheimer's disease (LOAD). It has been proposed that at least two other polymorphisms in the promoter of the APOE gene (-219G>T and -491A>T) might also contribute to disease susceptibility, and modulate the impact of structural changes in the ApoE protein, by altering its expression. In order to assess the extent of cis-acting influences on APOE expression in human brain, highly quantitative measures of allele discrimination were applied to cortical RNA from individuals heterozygous for the epsilon alleles. A small, but significant, increase in the expression of epsilon4 allele was observed relative to that of the epsilon3 and epsilon2 alleles (PT promoter polymorphism revealed significantly lower relative expression of haplotypes containing the -219T allele (P=0.02). Our data indicate that, in human brain, most of the cis-acting variance in APOE expression is accounted for by the epsilon4 haplotype, but there are additional, small, cis-acting influences associated with promoter genotype.