Wu Ping, Li Hong-Lei, Liu Zhi-Jun, Tao Qing-Qing, Xu Miao, Guo Qi-Hao, Hong Zhen, Sun Yi-Min
Department of Neurology and Institute of Neurology, Fudan University, Shanghai, People's Republic of China ; PET Center, Department of Nuclear Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
Department of Neurology and Institute of Neurology, Fudan University, Shanghai, People's Republic of China.
Clin Interv Aging. 2015 Jan 30;10:371-8. doi: 10.2147/CIA.S73396. eCollection 2015.
Apolipoprotein E gene (APOE) polymorphisms contributing to the risk of sporadic Alzheimer's disease (AD) have been identified for decades, but it has not been investigated in large AD samples of Chinese Han population.
We performed a cross-sectional study to explore the effect of APOE polymorphisms on sporadic AD in 875 sporadic AD patients and 1,195 cognitive normal controls of Chinese Han. Genotyping of APOE was determined by multiplex amplification refractory mutation system polymerase chain reaction.
APOE ε3ε4 and ε4ε4 genotypes increased AD risk with dosage effect. The odds ratio (OR) of ε3ε4 was 1.89 and the OR of ε4ε4 was 15.64 compared with that of ε3ε3 in all the subjects. E2ε3 genotype decreased AD risk in all the subjects (OR=0.64), female subgroup (OR=0.57), and late-onset AD subgroup (OR=0.60). However, neither ε2ε2 nor ε2ε4 affected AD risk. About the age at onset (AAO), the influence of APOE ε4 was only exhibited in late-onset AD subgroup, with 1 year lower in ε4-positive ones than negative ones. Further analysis did not show the dosage effect of ε4 pertinent to AAO, though the AAO of ε4ε4 patients decreased by 2 years. E2 did not affect the AAO of AD.
APOE ε4 is a strong risk factor of AD risk in Chinese Han population, and APOE ε4ε4 genotype might be related to the AAO of late-onset AD.
载脂蛋白E基因(APOE)多态性与散发性阿尔茨海默病(AD)风险的关系已被确认数十年,但尚未在中国汉族人群的大样本AD研究中进行调查。
我们进行了一项横断面研究,以探讨APOE多态性对875例散发性AD患者和1195例认知正常的中国汉族对照者的散发性AD的影响。通过多重扩增阻滞突变系统聚合酶链反应确定APOE的基因分型。
APOE ε3ε4和ε4ε4基因型以剂量效应增加AD风险。在所有受试者中,ε3ε4的优势比(OR)为1.89,ε4ε4的OR为15.64,与ε3ε3相比。E2ε3基因型在所有受试者(OR = 0.64)、女性亚组(OR = 0.57)和晚发性AD亚组(OR = 0.60)中降低了AD风险。然而,ε2ε2和ε2ε4均未影响AD风险。关于发病年龄(AAO),APOE ε4的影响仅在晚发性AD亚组中表现出来,ε4阳性者比阴性者低1年。进一步分析未显示ε4与AAO相关的剂量效应,尽管ε4ε4患者的AAO降低了2年。E2不影响AD的AAO。
APOE ε4是中国汉族人群AD风险的强危险因素,APOE ε4ε4基因型可能与晚发性AD的AAO有关。