Isoform of APOE with retained intron 3; quantitation and identification of an associated single nucleotide polymorphism.
Isoform of APOE with retained intron 3; quantitation and identification of an associated single nucleotide polymorphism.
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DOI：
10.1186/1750-1326-5-34
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发表时间：
2010-09-07
影响因子：
15.1
通讯作者：
Estus S
中科院分区：
文献类型：
--
作者：
Dieter LS;Estus S
载脂蛋白E（APOE）等位基因是晚发性阿尔茨海默病（LOAD）的主要遗传危险因素。最近，一种保留内含子3的APOE剪接变体（APOE-I3）被鉴定出来。为了深入了解这种亚型在LOAD中的可能作用，我们通过使用定量RT-PCR在56个人脑标本的队列中定量其表达。我们发现，APOE-I3通常占总APOE表达的低百分比（<0.5%）。然而，在一份标本中，APOE-I3的比例增加了约13倍。该样本在队列中是独一无二的，因为它具有内含子3单核苷酸多态性（SNP）的次要等位基因rs12982192。此外，一项等位基因表达失衡研究表明，rs12982192次要等位基因与APOE-I3表达增加相关。总的来说，我们解释我们的结果表明，APOE-I3代表一小部分的APOE表达和rs12982192与APOE内含子3保留。由于该SNP的次要等位基因与rs429358的次要等位基因（其定义了APOE4等位基因）在相同的单倍型上，我们推测rs12982192可能反映了编码功能性APOE4的mRNA的适度丢失。
Alleles of apolipoprotein E (APOE) are the major genetic risk factor for late onset Alzheimer's Disease (LOAD). Recently, an APOE splice variant that retains intron 3 (APOE-I3) was identified. To gain insight into the possible role of this isoform in LOAD, we quantified its expression in a cohort of 56 human brain specimens by using quantitative RT-PCR. We found that APOE-I3 generally represents a low percentage (< 0.5%) of overall APOE expression. However, in one specimen, the proportion of APOE-I3 was increased about ~13 fold. This specimen was unique in the cohort for possessing the minor allele of an intron 3 single nucleotide polymorphism (SNP), rs12982192. Additionally, an allelic expression imbalance study indicated that the rs12982192 minor allele was associated with increased APOE-I3 expression. Overall, we interpret our results as suggesting that APOE-I3 represents a minor portion of APOE expression and that rs12982192 is associated with APOE intron 3 retention. Since the minor allele of this SNP is on the same haplotype as the minor allele of rs429358, which defines the APOE4 allele, we speculate that rs12982192 may reflect a modest loss of mRNA encoding functional APOE4.
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影响因子：
16.2
作者：
Kim, Jungsu;Basak, Jacob M.;Holtzman, David M.
通讯作者：
Holtzman, David M.
影响因子：
34.7
作者：
Bu, Guojun
通讯作者：
Bu, Guojun
DOI：
10.1016/0005-2760(87)90295-5
发表时间：
1987-01-13
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
PITAS, RE;BOYLES, JK;MAHLEY, RW
通讯作者：
MAHLEY, RW
影响因子：
3.5
作者：
Zou, Fanggeng;Gopalraj, Rangaraj K.;Estus, Steven
通讯作者：
Estus, Steven
影响因子：
15.9
作者：
BOYLES, JK;PITAS, RE;TAYLOR, JM
通讯作者：
TAYLOR, JM