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APOEε4等位基因升高炎症因子表达并促进阿尔茨海默病进展:基于温州地区汉族和畲族人群的比较研究

APOE ε4 allele elevates the expressions of inflammatory factors and promotes Alzheimer's disease progression: A comparative study based on Han and She populations in the Wenzhou area.

作者信息

Fan Yin-Ying, Cai Qiao-Le, Gao Zhi-Yong, Lin Xue, Huang Qi, Tang Wei, Liu Jia-Hong

机构信息

Psychiatry Department, Wenzhou Kangning Hospital, Wenzhou 325000, Zhejiang Province, PR China.

Psychiatry Department, Wenzhou Kangning Hospital, Wenzhou 325000, Zhejiang Province, PR China.

出版信息

Brain Res Bull. 2017 Jun;132:39-43. doi: 10.1016/j.brainresbull.2017.04.017. Epub 2017 Apr 29.

Abstract

OBJECTIVE

This study aimed to investigate the impact of apolipoprotein E 4 (APOE4) gene polymorphisms on the expressions of inflammatory factors and the progression of Alzheimer's disease (AD).

METHODS

A total of 185 AD patients (the case group, 130 cases from the Han ethnic group and 55 cases from the She ethnic group) and 190 healthy individuals (the control group, 130 cases from the Han ethnic group and 60 cases from the She ethnic group) were recruited for our study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was conducted to detect APOE4 genotype and allele frequency. Enzyme-linked immunosorbent assay (ELISA) was used to determine the expressions of inflammatory factors in plasma.

RESULTS

In both Han and She populations, the frequency of ε3/4 and ε4/4 genotypes and the ε4 allele was significantly higher in the case group than that in the control group. ε3/4 and ε4/4 genotypes and the ε4 allele were the risk factors for AD. In both Han and She populations, the ε2/4, ε3/4 and ε4/4 carriers showed increased levels of TNF-α, IL-6, and IL-1β when compared with the ε2/2 + ε2/3 + ε3/3 carriers. The TNF-α, IL-6, and IL-1β levels were higher in the ε4/4 carriers than those in the ε2/4 and ε3/4 carriers, and ε2/4, ε3/4 and ε4/4 carriers in the case group exhibited increased levels of TNF-α, IL-6, and IL-1β when compared with the control group (P<0.05). Logistic regression analysis indicated that the ε3/4 genotype and TNF-α, IL-6, and IL-1β levels were associated with the susceptibility to AD in the Han population, while ε3/4 and ε4/4 genotypes and TNF-α, IL-6, and IL-1β levels were related to the susceptibility to AD in the She population.

CONCLUSIONS

The APOE4 ε4 allele may enhance susceptibility to AD and promotes the expressions of inflammatory factors in AD.

摘要

目的

本研究旨在探讨载脂蛋白E4(APOE4)基因多态性对炎症因子表达及阿尔茨海默病(AD)进展的影响。

方法

本研究共纳入185例AD患者(病例组,汉族130例,畲族55例)和190例健康个体(对照组,汉族130例,畲族60例)。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)检测APOE4基因型和等位基因频率。采用酶联免疫吸附测定(ELISA)法测定血浆中炎症因子的表达。

结果

在汉族和畲族人群中,病例组ε3/4和ε4/4基因型及ε4等位基因频率均显著高于对照组。ε3/4和ε4/4基因型及ε4等位基因是AD的危险因素。在汉族和畲族人群中,与ε2/2 + ε2/3 + ε3/3携带者相比,ε2/4、ε3/4和ε4/4携带者的TNF-α、IL-6和IL-1β水平升高。ε4/4携带者的TNF-α、IL-6和IL-1β水平高于ε2/4和ε3/4携带者,病例组中ε2/4、ε3/4和ε4/4携带者的TNF-α、IL-6和IL-1β水平高于对照组(P<0.05)。Logistic回归分析表明,ε3/4基因型及TNF-α、IL-6和IL-1β水平与汉族人群AD易感性相关,而ε3/4和ε4/4基因型及TNF-α、IL-6和IL-1β水平与畲族人群AD易感性相关。

结论

APOE4 ε4等位基因可能增加AD易感性并促进AD中炎症因子的表达。

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