A cluster of cholesterol-related genes confers susceptibility for Alzheimer's disease
A cluster of cholesterol-related genes confers susceptibility for Alzheimer's disease
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DOI：
10.4088/jcp.v66n0720
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发表时间：
2005-07-01
影响因子：
5.3
通讯作者：
Hock, C
中科院分区：
文献类型：
--
作者：
Papassotiropoulos, A;Wollmer, MA;Hock, C
目的：多基因疾病与遗传变异的复杂相互作用有关。我们评估了胆固醇和脂质相关的遗传变异簇是否与阿尔茨海默病有关。方法：对545名研究对象（阿尔茨海默病组284例，对照组261例）的12个胆固醇相关单核苷酸多态性和48个对照多态性进行分析。根据NINCDS-ADRDA标准诊断阿尔茨海默病。采用集合关联法进行多位点遗传关联分析。数据收集日期为2000年1月至2003年12月。结果：我们在APOE、SOAT1、APOE 5'-未传递区、OLR1、CYP46A1、LPL、LIPA和APOA4中发现了一组多态性，这些多态性赋予了阿尔茨海默病的显著易感性（p = 0.0002）。该基因簇的诊断准确率达到74%，与脑脊液中脑胆固醇分解代谢物24s -羟基胆固醇水平显著相关（p = 0.018）。结论：我们的研究结果建立了一种识别疾病相关遗传簇的新方法，并证明了在复杂疾病的遗传学中需要多位点方法。
Objective: Polygenic diseases are related to the complex interplay of genetic variations. We evaluated whether clusters of cholesterol- and lipid-related genetic variations are associated with Alzheimer's disease.Method: We analyzed 12 cholesterol-related single nucleotide polymorphisms and 48 control polymorphisms in 545 study participants (Alzheimer's disease group N = 284; control group N = 261). Diagnoses of Alzheimer's disease were made according to the NINCDS-ADRDA criteria. Multi-locus genetic association analysis was done with the set-association method. Dates of data collection were from January 2000 to December 2003.Results: We identified a cluster of polymorphisms in APOE, SOAT1, APOE 5'-untransiated region, OLR1, CYP46A1, LPL LIPA, and APOA4 conferring significant (p =.0002) susceptibility for Alzheimer's disease. This gene cluster reached a diagnostic accuracy of 74% and correlated significantly (p =.018) with the levels of the brain cholesterol catabolite 24S-hydroxycholesterol in the cerebrospinal fluid.Conclusion: Our results establish a novel approach for the identification of disease-related genetic clusters and demonstrate the need for multilocus methods in the genetics of complex diseases.