Abstract:

Objective　To investigate the relationship of apolipoprotein E (ApoE) genotype with blood lipids and cognitive function in patients with Alzheimer's disease (AD). Methods　One hundred and seven patients with AD treated at Yan 'an People's Hospital from March 2022 to May 2023 were selected as a study group. According to the severity of cognitive function, the patients were divided into a severe group (25 cases; the score of Mini-Mental State Examination (MMSE) ≤9) and a mild to moderate group (82 cases; the score of MMSE 10-26). Fifty-two healthy examinees during the same period at Yan 'an People's Hospital were selected as a control group. There were 61 males and 46 females in the study group who were (63.17±8.35) years old. There were 33 males and 19 females in the control group who were (63.86±8.02) years old. The ApoE genotype and allele frequency distribution and blood lipid levels [triglyceride (TG), high density lipoprotein cholesterol (HDL-C), cholesterol (CHO), and low density lipoprotein cholesterol (LDL-C)] in the patients with different ApoE alleles were compared between the control group, the mild to moderate group, and the severe group. The correlation between serum lipid levels and ApoE alleles in the patients was analyzed. The clinical data of the mild to moderate group and the severe group were compared. The influencing factors of severe cognitive dysfunction in the patients were analyzed. χ², t, and F tests were applied. Results　The gene distribution in the control group, the mild to moderate group, and the severe group was consistent with the Hardy-Weinberg equilibrium law (=0.83, 2.46, and 0.50; all P>0.05), indicating population representation. The ApoE 3/4 ε2/4 and ε3/4 genotypes of the severe group were higher than those of the mild to moderate group (both P<0.05). The ApoEε4 allele in the severe group was higher than those in the mild-moderate group and the control group; the ApoEε3 allele in the severe group was lower than those in the mild-moderate group and the control group; the ApoEε3 allele in the mild-moderate group was lower than that in the control group (all P<0.05). There was no statistical difference in ApoEε2 allele between the the severe group and the mild-moderate group (P>0.05), but the ApoEε2 allele in the severe group and the mild-moderate group were higher than that in that in the control group (both P<0.05). The Spearman analysis showed that TG, HDL-C, CHO, and LDL-C were not correlated with ApoE alleles (all P>0.05). The interleukin-6 (IL-6) and lipoprotein phospholipase A2 (Lp-PLA2) in the severe group were higher than those in the mild-moderate group (both P<0.05). The multivariate logistic regression analysis showed that the ApoEε4 allele (OR=3.924, 95%CI 1.725-8.925) and Lp-PLA2 (OR=2.807, 95%CI 1.234-6.385) were the influential factors for severe cognitive impairment in the patients (both P<0.05). Conclusions　ApoE alleles are not associated with lipid levels in patients with AD. AD patients with ApoE epsilon 4 have a higher risk of severe cognitive impairment.

Key words:

Alzheimer's disease, Apolipoprotein E, Genotype, Blood lipids, Cognitive function

摘要：

目的　探讨阿尔茨海默病（AD）载脂蛋白E（ApoE）基因型与血脂、认知功能的关系。方法　前瞻性选择2022年3月至2023年5月延安市人民医院收治的107例AD患者作为研究组，根据患者认知功能严重程度分为重度组［25例，简明精神状态评估量表（MMSE）评分≤9分］与轻中度组（82例，MMSE评分10～26分）；另选择医院同时间段52名健康体检者作为对照组。研究组男61例，女46例；年龄（63.17±8.35）岁。对照组男33名，女19名；年龄（63.86±8.02）岁。对比对照组、轻中度组、重度组ApoE基因型及等位基因频率分布情况、不同ApoE等位基因AD患者血脂水平［甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）、胆固醇（CHO）、低密度脂蛋白胆固醇（LDL-C）］，分析血脂水平与AD患者ApoE等位基因的相关性；对比轻中度组与重度组临床资料，分析AD患者合并重度认知功能障碍的影响因素。统计学方法采用χ²检验、t检验、F检验。结果　对照组、轻中度组、重度组基因分布均符合Hardy-Weinberg平衡定律（χ²=0.83、2.46、0.50，均P>0.05），具有群体代表性。重度组ApoEε3/4基因型高于轻中度组，重度组ApoEε2/4、ε3/4基因型均高于对照组（均P<0.05）。重度组ApoEε4等位基因高于轻中度组、对照组，重度组ApoEε3等位基因低于轻中度组、对照组，轻中度组ApoEε3等位基因低于对照组（均P<0.05）；重度组与轻中度组ApoEε2等位基因比较，差异无统计学意义（P>0.05），重度组、轻中度组ApoEε2等位基因均高于对照组（均P<0.05）。Spearman分析结果显示，TG、HDL-C、CHO、LDL-C与ApoE等位基因均无相关性（均P>0.05）。重度组白细胞介素-6（IL-6）、脂蛋白磷脂酶A2（Lp-PLA2）高于轻中度组（均P<0.05）。多因素logistic回归分析结果显示，携带ApoEε4等位基因（OR=3.924，95%CI 1.725～8.925）、Lp-PLA2（OR=2.807，95%CI 1.234～6.385）均为AD患者合并重度认知功能障碍的影响因素（均P<0.05）。结论　ApoE等位基因与AD患者血脂水平无相关性，携带ApoEε4等位基因的AD患者合并重度认知功能障碍的风险更高。

关键词:

阿尔茨海默病, 载脂蛋白E, 基因型, 血脂, 认知功能