A polymorphism in lipoprotein lipase affects the severity of Alzheimer's disease pathophysiology
A polymorphism in lipoprotein lipase affects the severity of Alzheimer's disease pathophysiology
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DOI：
10.1111/j.1460-9568.2006.05007.x
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发表时间：
2006-09-01
影响因子：
3.4
通讯作者：
Poirier, Judes
中科院分区：
文献类型：
--
作者：
Blain, Jean-Francois;Aumont, Nicole;Poirier, Judes
新出现的证据表明脂蛋白脂酶（LPL）在退行性疾病中的作用。LPL基因的遗传变异以前与脂质失衡和冠状动脉疾病（CAD）的风险和严重程度相关，这种疾病与常见的阿尔茨海默病（AD）具有共同的病理特征。为了评估这些遗传变异是否与常见AD的风险和病理生理学相关，对尸检证实的患者（242例对照，153例AD）进行LPL PvuII单核苷酸多态性（SNP; rs 285;称为P+等位基因）基因分型。测定脑LPL mRNA水平、胆固醇水平、淀粉样蛋白浓度、老年斑和神经纤维缠结密度计数，并与特定LPL基因型进行对比。当调整年龄和性别时，P+等位基因的纯合性导致AD风险的比值比为2.3。更重要的是，我们报道了LPL的P+等位基因的存在显著影响其mRNA表达水平（n = 51; P = 0.026）、脑组织胆固醇水平（n = 55; P = 0.0013）、神经元缠结（n = 52; P = 0.025）和老年斑（n = 52; P = 0.022）密度。这些结果表明，脂蛋白脂酶基因的一个共同的多态性调节的风险水平，散发性AD在加拿大东部的人口，但更重要的是，间接调节尸检证实的情况下，大脑的病理生理。
Emerging evidences indicate a role for lipoprotein lipase (LPL) in degenerative states. Genetic variations in the LPL gene were previously associated to lipid imbalance and coronary artery disease (CAD) risk and severity, a condition that shares pathological features with common Alzheimer's disease (AD). To evaluate whether these genetic variations associate with the risk and pathophysiology of common AD, autopsy-confirmed patients (242 controls, 153 AD) were genotyped for a PvuII single nucleotide polymorphism (SNP; rs285; referred to as the P+ allele) of LPL. Brain LPL mRNA levels, cholesterol levels, amyloid concentration, senile plaques and neurofibrillary tangles density counts were measured and contrasted with specific LPL genotypes. When adjusted for age and sex, homozygosity for the P+ allele resulted in an odds ratio of 2.3 for the risk of developing AD. More importantly, we report that the presence of the P+ allele of LPL significantly affects its mRNA expression level (n = 51; P = 0.026), brain tissue cholesterol levels (n = 55; P = 0.0013), neurofibrillary tangles (n = 52; P = 0.025) and senile plaque (n = 52; P = 0.022) densities. These results indicate that a common polymorphism in the lipoprotein lipase gene modulates the risk level for sporadic AD in the eastern Canadian population but more importantly, indirectly modulates the pathophysiology of the brain in autopsy-confirmed cases.