APOE genotype and cholesterol levels in Lewy body dementia and Alzheimer disease: Investigating genotype-phenotype effect on disease risk
APOE genotype and cholesterol levels in Lewy body dementia and Alzheimer disease: Investigating genotype-phenotype effect on disease risk
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DOI：
10.1097/01.jgp.0000225088.29353.08
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发表时间：
2006-12-01
影响因子：
7.2
通讯作者：
Padovani, Alessandro
中科院分区：
文献类型：
--
作者：
Borroni, Barbara;Grassi, Mario;Padovani, Alessandro
背景载脂蛋白E是散发性迟发性阿尔茨海默病（AD）最公认的遗传危险因素。载脂蛋白E基因型在路易体痴呆（LBD）中的作用以及载脂蛋白E基因型与胆固醇水平之间的关系仍不清楚。目的：本研究的目的是探讨载脂蛋白E基因型与LBD和AD患者胆固醇水平的关系。方法：连续入选82例LBD患者，以及数量相当的AD患者和对照组。结果：APOE基因型在AD和LBD患者中的分布与对照组相比有显著性差异，且APOE基因型以APOE基因型<$4+（<$4 +/<$4+或<$4 +/<$4）多见。不同的模型已被拟合，总APOE β 4-高胆固醇血症的完全交互作用的效果，声称在预测其对疾病的结果的关系。与对照组和LBD患者相比，高胆固醇血症和APOE β 4等位基因杂合子患者发生AD的风险超过3倍。高胆固醇血症和APOE β 4纯合子受试者发生AD的风险是对照组和LBD受试者的13倍。相反，在LBD和对照组中，没有证据表明APOE β 4-高胆固醇血症完全相互作用。结论：这项研究强调，APOE不仅是AD的危险因素，也是LBD的危险因素，而且APOE-胆固醇途径对AD和LBD的影响不同。这种方法可能有助于识别APOE基因型和可改变的危险因素的相互作用，即，高胆固醇血症，最终导致风险受试者的个体化和有效的降胆固醇治疗。
Background. APOE is the most recognized genetic risk factor for sporadic late-onset Alzheimer disease (AD). The role of APOE genotype in Lewy body dementia (LBD) is still unknown as well as the relationship between APOE genotype and cholesterol levels. Objective: The objective of this study was to explore the association between APOE genotype and cholesterol levels in patients with LBD and those with AD. Methods: Eighty-two patients with LBD were consecutively enrolled as well as a comparable number of patients with AD and comparison group. Each subject underwent a clinical and neuropsychologic evaluation and APOE genotyping, Results: The distribution of APOE genotypes signficantly differed between AD and LBD cases compared with the comparison group, with the APOE epsilon 4+ (epsilon 4+/epsilon 4+ or epsilon 4+/epsilon 4) genotype more frequent inpatient subgroups. Different models have been fitted, and total APOE epsilon 4-hypercholesterolemia complete interaction effect was claimed in predicting their relationship on disease outcome. Subjects with hypercholesterolemia and heterozygous for APOE epsilon 4 allele had more than threefold risk to develop AD compared both with the comparison group and with those with LBD. The risk to develop AD in hypercholesterolemic and APOE epsilon 4 homozygous subjects was 13-fold compared with the comparison group and those with LBD. Conversely, there was not evidence for APOE epsilon 4-hypercholesterolemia complete interaction effect in LBD and in the comparison group. Conclusions: This study highlighted that APOE is a risk factor not only for AD, but also for LBD, and that the APOE-cholesterol pathway differently affects AD and LBD. This approach may aid the search for the identification of an interactive effect of APOE genotype and modifiable risk factors, i.e., hypercholesterolemia, eventually resulting in individualized and effective cholesterol-lowering therapy in at-risk subjects.