Association between apolipoprotein E gene polymorphism and nonalcoholic fatty liver disease in Southern China: A case‐control study

Liu, Sudong; Weng, Ruiqiang; Gu, Xiaodong; Li, Lihai; Zhong, Zhixiong

doi:10.1002/jcla.24061

Cited by 8 publications

(5 citation statements)

References 33 publications

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“…While early observational studies investigating the relation of the APOE polymorphism and the risk of fatty liver disease, or NAFLD in particular, hardly find any significance [ 35 - 37 ], Sazci et al reported an apparent accumulation of APOE epsilon 3 homozygotes in NASH patients in 2008 [ 38 ]. This finding was then corroborated in case-control studies [ 39 , 40 ] identifying APOE epsilon 4 as the protective allele. Since then, several genome- and exome-wide association analyses have been confirming an association of the APOE4/APOE3-distinguishing SNP (rs429358) with liver function, liver fat content and fatty liver disease on different ethnic backgrounds [ 41 - 45 ].…”

Section: Introductionsupporting

confidence: 53%

Human APOE4 Protects High-Fat and High-Sucrose Diet Fed Targeted Replacement Mice against Fatty Liver Disease Compared to APOE3

Huebbe,

Bilke,

Rueter

et al. 2024

Aging and disease

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Recent genome- and exome-wide association studies suggest that the human APOE ε4 allele protects against non-alcoholic fatty liver disease (NAFLD), while ε3 promotes hepatic steatosis and steatohepatitis. The present study aimed at examining the APOE genotype-dependent development of fatty liver disease and its underlying mechanisms in a targeted replacement mouse model. Male mice expressing the human APOE3 or APOE4 protein isoforms on a C57BL/6J background and unmodified C57BL/6J mice were chronically fed a high-fat and high-sucrose diet to induce obesity. After 7 months, body weight gain was more pronounced in human APOE than endogenous APOE expressing mice with elevated plasma biomarkers suggesting aggravated metabolic dysfunction. APOE3 mice exhibited the highest liver weights and, compared to APOE4, massive hepatic steatosis. An untargeted quantitative proteome analysis of the liver identified a high number of proteins differentially abundant in APOE3 versus APOE4 mice. The majority of the higher abundant proteins in APOE3 mice could be grouped to inflammation and damage-associated response, and lipid storage, amongst others. Results of the targeted qRT-PCR and Western blot analyses contribute to the overall finding that APOE3 as opposed to APOE4 promotes hepatic steatosis, inflammatory- and damage-associated response signaling and fibrosis in the liver of obese mice. Our experimental data substantiate the observation of an increased NAFLD-risk associated with the human APOEε3 allele, while APOEε4 appears protective. The underlying mechanisms of the protection possibly involve a higher capacity of nonectopic lipid deposition in subcutaneous adipose tissue and lower hepatic pathogen recognition in the APOE4 mice.

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Section: Introductionsupporting

confidence: 53%

Human APOE4 Protects High-Fat and High-Sucrose Diet Fed Targeted Replacement Mice against Fatty Liver Disease Compared to APOE3

Huebbe,

Bilke,

Rueter

et al. 2024

Aging and disease

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“…Groups of continuous data analysis were performed with Mann-Whitney U -test. The allele (ε2, ε3, ε4) and genotype (E2/E2, E2/E3, E2/E4, E3/E3, E3/ E4, E4/E4) are respectively of the control group (without CVD or tumor) as a reference [ 51 – 53 ]. Chi-square test was performed for comparing allele frequencies composition ratios.…”

Section: Methodsmentioning

confidence: 99%

Effects of APOE gene ε4 allele on serum lipid profiles and risk of cardiovascular disease and tumorigenesis in southern Chinese population

et al. 2022

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Background Human apolipoprotein E (APOE) polymorphisms are attributable to the presence of three common alleles, namely, ε2, ε3, and ε4, which generate six genotypes, viz, E2/E2, E2/E3, E3/E3, E3/E4, E4/E4, and E2/E4. APOE polymorphisms are associated with all types of tumors and cardiovascular diseases (CVD). However, the relationship between the type of APOE polymorphisms and tumorigenesis remains debatable. Therefore, we aimed to investigate the role of APOE polymorphisms on the tumor with or without CVD in southern China. Methods A total of 1438 participants were categorized into 4 groups: 409 patients with tumor, 369 patients with CVD, 338 patients with both tumor and CVD, and 322 controls. APOE polymorphisms were determined by genotyping assay. The factors influencing tumor patients with or without CVD were also analyzed by logistic regression analysis. Results The present study involved different types of solid tumors. Lung cancer was the most common cancer (20.2%, 151/747), followed by colorectal (17%, 127/747), esophageal (9.8%, 73/747), and liver (8.7%, 65/747) cancers. E3/E3 was the most frequent genotype, and ɛ3 was the greatest allele frequency in our study population. The frequencies of the E3/E3, E3/E4, E2/E3, E2/E4, E4/E4, and E2/E2 genotypes in tumor patients were 76.97% (575/747), 14.19% (106/747), 6.83% (51/747), 1.2% (9/747), 0.4% (3/747), and 0.4% (3/747), respectively. Tumor patients carrying ε3 with or without CVD showed higher levels of TG, TC, and LDL-C and lower levels of HDL-C compared to the controls carrying ε3. On the other hand, the tumor patients carrying ε4 with or without CVD showed higher levels of TG and LDL-C and lower levels of HDL-C (all P < 0.05). The frequency of APOE ε4 allele and the E3/E4 genotype was relatively greater in tumor or CVD patients (P < 0.001). In addition, ε4 allele acted as an independent risk factor for tumor patients group (P = 0.037, adjusted OR = 1.92, 95% CI 1.04–3.55) and tumor + CVD patients group (P = 0.012, adjusted OR = 2.53, 95% CI 1.22–5.23). Conclusions Individuals carrying ε4 are at a higher risk of tumor with or without CVD, and APOE polymorphisms affect the serum lipid profiles.

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“…Hyperglycemia affects the distribution of tight-junction (TJ) proteins and nutrient transporters across the BBB, altering its permeability and function as shown in in vitro models [ 75 ] and magnetic resonance imaging (MRI) in patients with T2DM [ 76 ]. The CNS effects of insulin resistance and diabetes were shown to be more marked in individuals with the apolipoprotein E alleles ε4 and ApoE-ε4 allele, which was found to be present in 16.6% of patients with NALFD [ 77 ].…”

Section: Molecular Evidencementioning

confidence: 99%

The Metabolic Impact of Nonalcoholic Fatty Liver Disease on Cognitive Dysfunction: A Comprehensive Clinical and Pathophysiological Review

Giuffrè,

Merli,

Pugliatti

et al. 2024

IJMS

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Nonalcoholic fatty liver disease (NAFLD) exponentially affects the global healthcare burden, and it is currently gaining increasing interest in relation to its potential impact on central nervous system (CNS) diseases, especially concerning cognitive deterioration and dementias. Overall, scientific research nowadays extends to different levels, exploring NAFLD’s putative proinflammatory mechanism of such dysmetabolic conditions, spreading out from the liver to a multisystemic involvement. The aim of this review is to analyze the most recent scientific literature on cognitive involvement in NAFLD, as well as understand its underlying potential background processes, i.e., neuroinflammation, the role of microbiota in the brain–liver–gut axis, hyperammonemia neurotoxicity, insulin resistance, free fatty acids, and vitamins.

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Association between apolipoprotein E gene polymorphism and nonalcoholic fatty liver disease in Southern China: A case‐control study

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 8 publications

References 33 publications

Human APOE4 Protects High-Fat and High-Sucrose Diet Fed Targeted Replacement Mice against Fatty Liver Disease Compared to APOE3

Human APOE4 Protects High-Fat and High-Sucrose Diet Fed Targeted Replacement Mice against Fatty Liver Disease Compared to APOE3

Effects of APOE gene ε4 allele on serum lipid profiles and risk of cardiovascular disease and tumorigenesis in southern Chinese population

The Metabolic Impact of Nonalcoholic Fatty Liver Disease on Cognitive Dysfunction: A Comprehensive Clinical and Pathophysiological Review

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