Association Study of Apolipoprotein E Gene Polymorphism With Incidence and Delayed Resolution of Hemifacial Spasm

Objective: This study investigates the correlation between Apolipoprotein E gene (APOE) polymorphism and the incidence and delayed resolution of hemifacial spasms.Methods: The APOE genotypes of 151 patients with hemifacial spasm and 73 control cases were determined by cleaved amplification polymorphism sequence-tagged sites. The distribution of three APOE alleles (ε2, ε3, and ε4) in two groups and the delayed resolution rate in 6 genotypes were calculated and statistically analyzed.Results: The proportion of patients with APOE ε3/ε4 genotype in the hemifacial spasm group (25.17%) was significantly higher than that in the control group (12.33%) (P = 0.027). In terms of allele frequency, the proportion of the APOE ε4 allele in the hemifacial spasm group (15.56%) was significantly higher than that in the control group (6.85%) (P = 0.009). Meanwhile, the proportion of APOE ε4 allele carriers in the hemifacial spasm group (29.80%) was significantly higher than that in the control group (13.7%) (P = 0.009). Logistic regression analysis showed that the ε4 allele significantly increased the incidence of hemifacial spasm (OR 2.675, 95%CI 1.260-5.678, P = 0.010). Among the 32 patients with a delayed resolution, the ε3/ε3 and ε3/ε4 had the highest proportion in 6 genotypes. The delayed resolution rate of APOE ε3/ε4 (34.21%) was significantly higher than APOE ε3/ε3 (17.78%) (P < 0.05). The delayed resolution rate of APOE ε4 carriers was the highest (33.33%) in the 3 allele carriers, but there was no significant difference among the 3 allele carriers (P = 0.065).Conclusion: The polymorphism of APOE is relevant to the incidence rate of hemifacial spasms. APOE ε4 allele increases the incidence of hemifacial spasm. The APOE ε4 allele may promote the occurrence of delayed resolution.

The Effect of Apolipoprotein E Gene Polymorphism and Lp (a) Levels on Coronary Artery Disease with Atrial Fibrillation

Background This study is the first to explore the influence of the apolipoprotein E gene (APOE) and blood lipid metabolism on coronary artery disease (CAD) with atrial fibrillation.Methods In this study, there were a total of 2048 participants, including 400 patients in the control group (CAD- AF-), 126 AF patients without CAD (CAD- AF+), 1294 CAD patients without AF (CAD+ AF-) and 228 CAD patients with AF (CAD+ AF+). Blood lipid levels and APOE genotypes were determined by collecting blood samples from the patients.Results Compared with CAD patients without AF, the age and Lp (a) levels of CAD patients with AF were significantly higher. Among CAD patients, the frequencies of E3/E3 and ε3 genotypes in patients with AF were significantly lower than those in patients without AF, and the frequencies of E4/E4 and ε4 genotypes were significantly increased. Spearman correlation analysis showed that in CAD patients, Lp(a) levels in the ε4 group were significantly higher than those in the group of patients without ε4, and there was a significant correlation between ε4 and Lp (a) levels (p<0.001, r=0.106). Multivariate logistic regression analysis found that the increase in Lp (a) levels (p=0.023) and age (p=0.01) were independent risk factors for CAD patients who develop AF.Conclusion Patients with AF had increased age, ε4 frequencies and Lp (a) levels among CAD patients, age and Lp (a) levels may be independent risk factors for CAD patients to develop AF.

The relationship between apolipoprotein E gene polymorphism and essential hypertension and the analysis of the efficacy of nanotechnology

The study aimed to detect the genetic polymorphism of apolipoprotein E (Apo E) in residents of Guizhou, China, explore its relationship with essential hypertension, and discuss the efficacy of nanotechnology in the treatment of hypertension. A total of 200 people in Guizhou, China were detected with Apo E polymorphisms and were divided into groups, The experimental group consists of people with essential hypertension and the control group of normal people. The SPSS 26.0 software was used to determine the correlation between Apo E gene polymorphisms and the essential hypertension risk. Logistic regression analysis was adopted to determine the risk factors of the Apo E gene for essential hypertension. Magnetic nanoparticles are used to help extract DNA, improve efficiency, and analyze the distribution of alleles in the population. The distribution frequencies of the six genotypes of E2/2, E2/3, E3/3, E3/4, E2/4, and E4/4 were 1.0%, 15.5%, 64.0%, 17.0%, 1.5%, and 1.0%, respectively, and the distribution frequencies of the three alleles of ε2, ε3, and ε4 were 9.5%, 80.3%, and 10.3%, respectively. There are more Apo E gene ε4 carriers in the experimental group than the control group, and the difference was statistically significant (P <0.05). The Apo E ε4 allele carriers had higher low-density lipoprotein and Apo B levels than the Apo E ε3 and Apo E ε2 gene carriers. Family history of hypertension and Apo E ε4 were both the main risk factors for essential hypertension. This study investigated the relationship between apolipoprotein E gene polymorphism and essential hypertension, and extracted DNA by magnetic nanoparticles to help analyze the distribution of alleles in hypertension population, which could provide theoretical basis for the diagnosis and treatment of essential hypertension in Guizhou Province, China.

Genetic influence of Apolipoprotein E gene ε2/ε3/ε4 isoforms on odds of mesial temporal lobe epilepsy

Objective: The potential correlation between the ε2/ε3/ε4 variants of the ApoE (Apolipoprotein E) gene and the odds of mesial temporal lobe epilepsy was investigated. Methods: The database searching for eligible studies was performed in October 2020. A series of pooling analyses were conducted. Results: We enrolled a total of twelve case-control studies for pooling. Within the pooling analysis of ε4, there was an in- creased risk of mesial temporal lobe epilepsy in cases under the models of carrier ε4 vs. ε3, ε3ε4 vs. ε3ε3, and ε3ε4+ε4ε4 vs. ε3ε3 [P < 0.05, odds ratio (OR) > 1], compared with controls. Moreover, we observed similar positive results in the subgroup analyses of “China” and “Population-based control” under the genetic models of ε4 (P < 0.05, OR > 1). Nevertheless, we did not detect the significant difference between the mesial temporal lobe epilepsy cases and controls in the pooling analyses of ε2 (all P > 0.05). Conclusion: The ε3ε4 genotype of ApoE seems to be linked to the risk of mesial temporal lobe epilepsy for patients in China. More sample sizes are required to confirm the potential role of ApoE isoforms in the susceptibility to diverse types of epilepsy from different origins. Keywords: Epilepsy; ApoE; isoforms; susceptibility.

Association of Apolipoprotein E Gene Polymorphism with Lipid Profile and Ischemic Stroke Risk in Type 2 Diabetes Mellitus Patients

Background. Altered lipid profiles have consistently been linked to cerebrovascular events. Ischemic stroke (IS) was a common comorbid condition established in type 2 diabetes mellitus (T2DM). The apolipoprotein E (ApoE) gene which has a notably critical function in lipoprotein metabolism is believed as one of the potential candidate genes susceptible to IS complications in T2DM. This research aimed to determine the association of apolipoprotein E gene polymorphism with lipid profile and IS risk in T2DM patients. Methods. This case-control study involved a total of 60 diabetic participants divided into two groups with and without IS. ApoE was genotyped using PCR and sequencing analysis. Results. The most predominant genotype observed in 27 participants (45%) was E3/E3. Lower levels of high-density lipoprotein cholesterol (HDL-C) were found in ε2 carriers ( p = 0.003 ; 95% CI −23.35–−4.89) and ε4 carriers ( p = 0.019 ; 95% CI 1.38–14.55) compared to ε3 homozygotes. Total cholesterol (TC), triglyceride, and low-density lipoprotein cholesterol (LDL-C) levels had no association with ApoE gene polymorphism in this study. ApoE gene polymorphism was not related to IS in T2DM ( p = 0.06 ; adjusted OR: 4.71; 95% CI 0.93–23.79). Conclusions. ApoE ε2 and ε4 carriers were associated with lower levels of HDL-C. No association was identified between ApoE gene polymorphism and IS in T2DM patients.

APOE4 disrupts intracellular lipid homeostasis in human iPSC-derived glia

The E4 allele of the apolipoprotein E gene (APOE) has been established as a genetic risk factor for many diseases including cardiovascular diseases and Alzheimer’s disease (AD), yet its mechanism of action remains poorly understood. APOE is a lipid transport protein, and the dysregulation of lipids has recently emerged as a key feature of several neurodegenerative diseases including AD. However, it is unclear how APOE4 perturbs the intracellular lipid state. Here, we report that APOE4, but not APOE3, disrupted the cellular lipidomes of human induced pluripotent stem cell (iPSC)–derived astrocytes generated from fibroblasts of APOE4 or APOE3 carriers, and of yeast expressing human APOE isoforms. We combined lipidomics and unbiased genome-wide screens in yeast with functional and genetic characterization to demonstrate that human APOE4 induced altered lipid homeostasis. These changes resulted in increased unsaturation of fatty acids and accumulation of intracellular lipid droplets both in yeast and in APOE4-expressing human iPSC-derived astrocytes. We then identified genetic and chemical modulators of this lipid disruption. We showed that supplementation of the culture medium with choline (a soluble phospholipid precursor) restored the cellular lipidome to its basal state in APOE4-expressing human iPSC-derived astrocytes and in yeast expressing human APOE4. Our study illuminates key molecular disruptions in lipid metabolism that may contribute to the disease risk linked to the APOE4 genotype. Our study suggests that manipulating lipid metabolism could be a therapeutic approach to help alleviate the consequences of carrying the APOE4 allele.