Fenoglio Chiara, Galimberti Daniela, Lovati Carlo, Guidi Ilaria, Gatti Alberto, Fogliarino Sergio, Tiriticco Marco, Mariani Claudio, Forloni Gianluigi, Pettenati Carla, Baron Pierluigi, Conti Giancarlo, Bresolin Nereo, Scarpini Elio
Department of Neurological Sciences, "Dino Ferrari" Center, University of Milan, IRCCS Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milan, Italy.
Neurobiol Aging. 2004 Oct;25(9):1169-73. doi: 10.1016/j.neurobiolaging.2003.11.008.
MCP-1 levels are increased in CSF of patients with Alzheimer's disease (AD) compared with controls, suggesting a role in the development of dementia. Recently, a biallelic A/G polymorphism in the MCP-1 promoter at position -2518 has been found, influencing the level of MCP-1 expression in response to an inflammatory stimulus. The distribution of the A-2518G SNP was determined in 269 AD patients and in 203 healthy age matched controls, showing no differences between the two groups. On the contrary, a significant increase of MCP-1 serum levels in AD patients carrying at least one G mutated allele was observed. Moreover, the highest peaks of MCP-1 serum levels were present in patients carrying two G alleles. Stratifying by ApoE genotype, gender or age at onset, no differences in both allele frequency and MCP-1 serum concentration were observed. The A-2518G polymorphism in MCP-1 gene does not seem to be a risk factor for the development of AD, but its presence correlates with higher levels of serum MCP-1, which can contribute to increase the inflammatory process occurring in AD.
与对照组相比,阿尔茨海默病(AD)患者脑脊液中的单核细胞趋化蛋白-1(MCP-1)水平升高,提示其在痴呆症发展过程中发挥作用。最近,在MCP-1启动子-2518位发现了一种双等位基因A/G多态性,它会影响MCP-1在炎症刺激下的表达水平。在269例AD患者和203例年龄匹配的健康对照中确定了A-2518G单核苷酸多态性(SNP)的分布,结果显示两组之间无差异。相反,观察到携带至少一个G突变等位基因的AD患者血清MCP-1水平显著升高。此外,携带两个G等位基因的患者血清MCP-1水平达到最高峰值。按载脂蛋白E(ApoE)基因型、性别或发病年龄分层后,等位基因频率和MCP-1血清浓度均无差异。MCP-1基因中的A-2518G多态性似乎不是AD发病的危险因素,但其存在与血清MCP-1水平升高相关,这可能会加剧AD中发生的炎症过程。