van Oijen Marieke, de Maat Moniek P M, Kardys Isabella, de Jong Frank Jan, Hofman Albert, Koudstaal Peter J, Witteman Jacqueline C, Breteler Monique M B
Department of Epidemiology & Biostatistics, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands.
Neurobiol Aging. 2007 Sep;28(9):1361-6. doi: 10.1016/j.neurobiolaging.2006.06.015. Epub 2006 Jul 18.
Inflammation plays a role in the pathogenesis of dementia and Alzheimer's disease (AD). Studies examining serum levels of C-reactive protein in relation to dementia yielded conflicting results. Since serum levels of C-reactive protein are partly determined by genetic factors, we examined the association between genetic variation in the C-reactive protein gene with dementia and AD.
This study was performed in the Rotterdam Study, a population-based prospective cohort study among elderly. Polymorphisms in the C-reactive protein gene (1184C>T, 2042C>T and 2911C>G) tagging the common haplotypes were genotyped and haplotypes were constructed. During follow-up (mean 9.2 years) 607 dementia cases were identified. We estimated the association between polymorphisms and haplotypes with dementia and AD with Cox' proportional hazard models.
The T allele of the C-reactive protein 2042C>T polymorphism, related to lower serum levels of C-reactive protein, was associated with a lower risk of dementia and AD. This association was strongest in APOE epsilon4 allele carriers.
These findings suggest that C-reactive protein plays a role in development of dementia.
炎症在痴呆和阿尔茨海默病（AD）的发病机制中起作用。研究血清C反应蛋白水平与痴呆的关系得出了相互矛盾的结果。由于血清C反应蛋白水平部分由遗传因素决定，我们研究了C反应蛋白基因的遗传变异与痴呆和AD之间的关联。
本研究在鹿特丹研究中进行，这是一项针对老年人的基于人群的前瞻性队列研究。对标记常见单倍型的C反应蛋白基因多态性（1184C>T、2042C>T和2911C>G）进行基因分型并构建单倍型。在随访期间（平均9.2年），确定了607例痴呆病例。我们用Cox比例风险模型估计多态性和单倍型与痴呆和AD之间的关联。
与较低血清C反应蛋白水平相关的C反应蛋白2042C>T多态性的T等位基因与较低的痴呆和AD风险相关。这种关联在APOEε4等位基因携带者中最强。
这些发现表明C反应蛋白在痴呆的发生发展中起作用。
