CYP46A1 and the APOEε4 Allele Polymorphisms Correlate with the Risk of Alzheimer's Disease
CYP46A1 and the APOEε4 Allele Polymorphisms Correlate with the Risk of Alzheimer's Disease
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DOI：
10.1007/s12035-018-0952-9
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发表时间：
2018-10-01
影响因子：
5.1
通讯作者：
Zhou, Hua-Dong
中科院分区：
文献类型：
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作者：
Li, Ling;Zeng, Fan;Zhou, Hua-Dong
胆固醇-24 S-羟化酶（CYP 46 A1）和载脂蛋白E（APOE）基因多态性是阿尔茨海默病（AD）的危险因素。胆固醇代谢产物24-羟基胆固醇（24-OHC）的血浆水平被认为与AD相关。本研究调查了AD患者中这些遗传因素与血液24-OHC和淀粉样蛋白β（A β）水平之间的相关性。采用关联分析、Logistic回归和线性回归分析CYP 46 A1和APOE基因型与血24-OHC和A β水平及AD风险的相关性。我们发现AD患者的APOE等位基因显著升高，并且在AD患者中CYP 46 A1 C等位基因和APOE等位基因之间存在潜在的协同作用。AD患者血24-OHC水平和A β水平明显高于对照组，提示24-OHC可作为AD诊断的一个指标。然而，具有CYP 46 A1 TT基因型而非CC基因型的AD患者具有更高的24-OHC水平，这表明CYP 46 A1多态性与AD的关系可能存在其他机制。
Polymorphisms of the cholesterol-24S-hydroxylase (CYP46A1) and apolipoprotein E (APOE) genes are risk factors for Alzheimer's disease (AD). Plasma level of 24S-hydroxcholesterol (24-OHC), the metabolite of cholesterol, is thought to correlate with AD. The present study investigated the correlation between these genetic factors and blood 24-OHC and amyloid-beta (A beta) levels in AD patients. Association analysis, logistic regression, and linear regression were used to analyze the correlation of CYP46A1 and APOE genotypes with blood 24-OHC and A beta levels and AD risk. We found that the APOE epsilon 4 alleles were significantly higher in patients with AD and there was a potential synergistic interaction between the CYP46A1 C allele and APOE epsilon 4 allele in AD. Blood 24-OHC level and A beta level were significantly higher in AD patients than controls, indicating 24-OHC could be a marker in AD diagnosis. However, AD patients with the CYP46A1 TT, but not CC, genotype had higher 24-OHC levels, which indicated that there may be other mechanisms in the relationship between CYP46A1 polymorphisms and AD.