Tumour necrosis factor-α gene polymorphisms and Alzheimer's disease
Tumour necrosis factor-α gene polymorphisms and Alzheimer's disease
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DOI：
10.1016/s0304-3940(03)00854-1
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发表时间：
2003-10-16
影响因子：
2.5
通讯作者：
Wilcock, GK
中科院分区：
文献类型：
--
作者：
Culpan, D;MacGowan, SH;Wilcock, GK
最近的研究结果表明，在阿尔茨海默病（AD）患者的大脑中，促炎细胞因子（如肿瘤坏死因子-α（TNF-α））的产生增加。我们使用直接测序方法对增强子/启动子区域的一部分和位于TNF-α基因上游10.5 kb的较小片段分别检测235例尸检证实的AD和130例对照病例的TNF-α多态性和TNF-α和-B微卫星等位基因。研究的TNF-α点突变或微卫星等位基因均未被证明是AD的独立危险因素。然而，当-308/A、-238/G和TNF-α 2作为2-1-2单倍型进行检查时，我们观察到该单倍型的缺失与AD显著相关（P = 0.014，Fisher精确检验），这表明2-1-2单倍型可能对AD具有保护作用。(C)2003爱思唯尔爱尔兰有限公司保留所有权利。
Recent findings suggest that production of pro-inflammatory cytokines, such as tumour necrosis factor-alpha (TNF-alpha), is increased in the brains of people with Alzheimer's disease (AD). We used direct sequencing methods on a section of the enhancer/promoter region and on a smaller fragment located 10.5 kb upstream of the TNF-alpha gene to respectively examine TNF-alpha polymorphisms and TNF-a and -b microsatellite alleles in a cohort of 235 post-mortem confirmed AD and 130 control cases. None of the TNF-alpha point mutations or microsatellite alleles investigated proved to be independent risk factors for AD. However, when -308/A, -238/G and TNF-a2 were examined as a 2-1-2 haplotype, we observed that the absence of that haplotype was significantly associated with AD (P = 0.014, Fisher's exact test) suggesting that the 2-1-2 haplotype may be protective against AD. (C) 2003 Elsevier Ireland Ltd. All rights reserved.