Protective effect of apolipoprotein E epsilon 3 on sporadic Alzheimer’s disease in the Chinese population: a meta-analysis
Authors: Chen Qian , Wang Ting , Kang Deying , Chen Lei 
Published: August 2022

Alzheimer’s disease (AD) is fast becoming one of the most expensive, deadly and burdensome diseases in this century. It has the fastest-growing disease burden in China. Apolipoprotein E (APOE) polymorphic alleles are generally considered to be the primary genetic determinant of AD risk: individuals with the E4 allele are at increased risk of AD compared with individuals with the more common E3 allele. Since the intensity of the association varies among different ethnic groups, a separate meta-analysis of the Chinese population is needed. We searched Chinese and English databases to sift through literature over the past 20 years. Data on the APOE genotype and AD were collected for correlation analysis. OR was calculated according to APOE allele and genotype. A publication bias analysis and sensitivity analysis were performed, and the main results were further verified by subgroup analysis. The 116 eligible studies enrolled 23,396 patients with AD and 25,568 healthy controls. The study subjects covered at least 30 of the 34 provincial-level administrative regions (including Taiwan). The partial sex ratio was as follows: AD male/female; 10,291/11,240; control male/female, 11,304/12,428, $${\upchi }^{2}$$

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= 0.122, P = 0.727. The results of the meta-analysis of alleles showed that I2 > 50% and Q statistics were significant for all genotypes; therefore, the random effect model was selected. The frequency of the ApoE ε4 allele in AD was higher than that in healthy controls, and the difference was statistically significant (OR 2.847, 95% CI [2.611–3.101], P < 0.001). The frequencies of ApoE ε3 and ε2 in AD were lower than those in healthy controls, and the differences were statistically significant (ε3: OR 0.539, 95% CI [0.504–0.576], P < 0.001; ε2: OR 0.771, 95% CI [0.705–0.843], P < 0.001). The results of the meta-analysis of AD genotype showed that ApoE ε2/ε4 (OR 1.521, 95% CI [1.270–1.823], P < 0.001), ε3/ε4 (OR 2.491, 95% CI [2.267–2.738], P < 0.001) and ε4/ε4 (OR 5.481, 95% CI [4.801–6.257], P < 0.001) allele genotype frequencies were higher than those of the healthy controls. The differences were all statistically significant. Moreover, the ApoE ε2/ε2 (OR 0.612, 95% CI [0.504–0.743], P < 0.001), ε2/ε3 (OR 0.649, 95% CI [0.585–0.714], P < 0.001) and ε3/ε3 (OR 0.508, 95% CI [0.468–0.551], P < 0.001) genotypes were less frequent in patients with AD than in healthy controls, and the differences were statistically significant. The results of the sensitivity analysis and subgroup analysis were consistent with those of the whole model. These results provide support for the protective effect of the ApoE ε3/ε3 genotype against the development of AD. This research is the most comprehensive meta-analysis of the correlation between APOE and AD in the Chinese population by analysing the distribution of the APOE gene in patients with AD reported in the last 20 years. It was concluded that the APOE ε3 allele had a protective effect against sporadic AD in the Chinese population, with great significance, and that its protective effect was stronger than that of the ε2 allele.