Variation in NPC1, the gene encoding Niemann-Pick C1, a protein involved in intracellular cholesterol transport, is associated with Alzheimer disease and/or aging in the Polish population.
Variation in NPC1, the gene encoding Niemann-Pick C1, a protein involved in intracellular cholesterol transport, is associated with Alzheimer disease and/or aging in the Polish population.
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DOI：
10.1016/j.neulet.2008.09.046
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发表时间：
2008-12-12
影响因子：
2.5
通讯作者：
Kuznicki, Jacek
中科院分区：
文献类型：
--
作者：
Erickson, Robert P.;Larson-Thome, Katherine;Weberg, Lyndon;Szybinska, Aleksandra;Mossakowska, Malgorzata;Styczynska, Maria;Barcikowska, Maria;Kuznicki, Jacek
大量证据表明，胆固醇代谢，特别是由细胞间转运蛋白APOE介导的胆固醇代谢，参与了散发性迟发性阿尔茨海默病（SLAD）的发病机制。参与SLAD发病机制的其他基因的鉴定受到阻碍，因为无论是个体还是全基因组的基因关联研究，都难以在多达25%或更多的正常成人中找到适当的对照。使用152名百岁老人作为额外的控制和120名“常规”，65至75岁的控制，我们显示了NPC 1的遗传变异与SLAD和/或衰老的关联。在这项初步研究中，我们发现梯度的两个非同义SNP的等位基因频率在NPC 1从百岁老人通过正常对照SLAD在这个非分层的波兰人口。干预内含子SNP不在Hardy-Weinberg平衡中，并且在百岁老人和对照/SLAD之间存在差异。通过fastPHASE确定的单倍型频率略有不同，预测的基因型频率在3组之间有很大差异。这些发现也可以解释为NPC 1在衰老中的作用，NPC 1在C. Dauer形成（冬眠，一种长寿状态）中的作用也表明了这一作用。优雅的
There is abundant evidence that cholesterol metabolism, especially as mediated by the intercellular transporter APOE, is involved in the pathogenesis of sporadic, late-onset Alzheimer disease (SLAD). Identification of other genes involved in SLAD pathogenesis has been hampered since gene association studies, whether individual or genome-wide, experience difficulty in finding appropriate controls in as much as 25% or more of normal adults will develop SLAD. Using 152 centenarians as additional controls and 120 “regular,” 65- to 75-year-old controls, we show an association of genetic variation in NPC1 with SLAD and/or aging. In this preliminary study, we find gradients of two non-synonymous SNP’s allele frequencies in NPC1 from centenarians through normal controls to SLAD in this non-stratified Polish population. An intervening intronic SNP is not in Hardy-Weinberg equilibria and differs between centenarians and controls/SLAD. Haplotypes frequencies determined by fastPHASE were somewhat different, and the predicted genotype frequencies were very different between the 3 groups. These findings can also be interpreted as indicating a role for NPC1 in aging, a role also suggested by NPC1’s role in Dauer formation (hibernation, a longevity state) in C. elegans.
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影响因子：
11.4
作者：
Crameri, A;Biondi, E;Mohajeri, MH
通讯作者：
Mohajeri, MH
影响因子：
12.7
作者：
Ding, ZT;Wang, Y;Hashizume, Y
通讯作者：
Hashizume, Y
DOI：
10.2174/1566524023362375
发表时间：
2002-08-01
期刊：
Current Molecular Medicine (Hilversum)
影响因子：
--
作者：
Garver, William S.;Heidenreich, Randall A.
通讯作者：
Heidenreich, Randall A.
影响因子：
--
作者：
Bales, K R;Dodart, J C;Paul, S M
通讯作者：
Paul, S M
神经元膜胆固醇损失增强了淀粉样蛋白肽的产生。
影响因子：
7.8
作者：
Abad-Rodriguez, Jose;Ledesma, Maria Dolores;Craessaerts, Katleen;Perga, Simona;Medina, Miguel;Delacourte, Andre;Dingwall, Colin;De Strooper, Bart;Dotti, Carlos G
通讯作者：
Dotti, Carlos G