APOC3 rs2070666 Is Associated with the Hepatic Steatosis Independently of PNPLA3 rs738409 in Chinese Han Patients with Nonalcoholic Fatty Liver Diseases

Zhang, Rui-Nan; Zheng, Rongqin; Mi, Yuqiang; Zhou, Detang; Shen, Feng; Chen, Guangyu; Zhu, Chan-Yan; Pan, Qin; Fan, Jian‐Gao

doi:10.1007/s10620-016-4120-7

Cited by 21 publications

(18 citation statements)

References 40 publications

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“…Zhou et al [14] have reported an association between polymorphisms on hepatic lipase and liver damage too. The APOC3 rs2070666 A allele is a risk factor for NAFLD independent of obesity, dyslipidemia, and PNPLA3 rs738409, and it might contribute to increased liver fat content [30]. Lipid metabolism is the cornerstone in NAFLD.…”

Section: Discussionmentioning

confidence: 99%

Cholesteryl Ester Transfer Protein Variant (RS1800777) with Liver Histology in Non-Alcoholic Fatty Liver Disease Patients

et al. 2018

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Introduction and Aims: Non-alcoholic fatty liver disease (NAFLD) is a spectrum of diseases ranging from simple steatosis without inflammation or fibrosis to nonalcoholic steatohepatitis and in the Western countries has become one of the most prevalent chronic liver diseases related to metabolic and lipid alterations. Cholesteryl ester transfer protein (CETP) participates in high density lipoprotein (HDL)-cholesterol metabolism. The aim of our study was to investigate the influence of polymorphism (rs1800777) of CETP gene on liver histological changes, biochemical parameters, and serum adipokines levels in patients with NAFLD. Material and Methods: A population of 90 patients with NAFLD was recruited in a cross-sectional study. A biochemical analysis (glucose, c-reactive protein, insulin, homeostasis model assessment-insulin resistance, total cholesterol, low density lipoprotein (LDL)-cholesterol, HDL-cholesterol, triglycerides blood, and adipokines (leptin, adiponectin, and resistin) was realized. Genotype of polymorphism (rs1800777) of CETP gene was studied. Results: Eighty-three patients (92.2%) had the genotype GG (wild type group) and 7 patients (7.8%) had the genotype GA (n = 7) or AA (n = 0; mutant type group). Patients with A allele show significant decrease in liver biochemistry parameters – Alanine amino transferase (delta 10.1 ± 9.9 UI/L; p = 0.01), aspartate aminotransferase activity (delta 13.3 ± 9.5 UI/L; p = 0.02), and gammaglutamine transferase levels (delta 39 ± 30.1 UI/L; p = 0.01). Logistic regression analysis indicated that subjects with A-allele carriers were associated with a decreased risk of lobulillar inflammation (OR 0.18, 95% CI 0.04–0.95, p = 0.04) and a decreased risk of steatosis (OR 0.13, 95% CI 0.02–0.89, p = 0.04). Conclusions: A variant of the polymorphism rs1800777 of CETP gene is independently associated with the presence of steatosis and lobulillar inflammation in subjects with proven biopsy NAFLD.

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Section: Discussionmentioning

confidence: 99%

Cholesteryl Ester Transfer Protein Variant (RS1800777) with Liver Histology in Non-Alcoholic Fatty Liver Disease Patients

et al. 2018

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“…PNPLA3 I148M and TM6SF2 E167K variations are closely related to the prevalence and severity of NAFLD. This group of NAFLD patients may not have characteristics of IR and MetS . Other independent risk factors for the occurrence and development of NAFLD include hyeruricemia, hyperhemoglobinemia, hypothyroidism, hypopituitarism, sleep apnea syndrome and polycystic ovary syndrome …”

Section: Epidemiology and Screeningmentioning

confidence: 99%

Guidelines of prevention and treatment of nonalcoholic fatty liver disease (2018, China)

Fan

Wei

Zhang

2018

J of Digest Diseases

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150

132

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“…Apo-CIII null mice fail to stimulate VLDL production upon HFD feeding, while Apo-CIII overexpressing mice show enhanced diet-induced triglyceride accumulation in the liver [ 129 ]. A genetic variant of Apo-CIII leads to enhanced circulating Apo-CIII in humans and is associated with NAFLD [ 130 ]. Hepatic Apo-CIII expression is suppressed by RARα via a pathway involving SHP and HNF4α, thereby reducing hepatic and plasma triglyceride levels [ 131 ].…”

Section: Vitamin a And Hepatic Lipid Metabolismmentioning

confidence: 99%

Disturbed Vitamin A Metabolism in Non-Alcoholic Fatty Liver Disease (NAFLD)

et al. 2017

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Vitamin A is required for important physiological processes, including embryogenesis, vision, cell proliferation and differentiation, immune regulation, and glucose and lipid metabolism. Many of vitamin A’s functions are executed through retinoic acids that activate transcriptional networks controlled by retinoic acid receptors (RARs) and retinoid X receptors (RXRs).The liver plays a central role in vitamin A metabolism: (1) it produces bile supporting efficient intestinal absorption of fat-soluble nutrients like vitamin A; (2) it produces retinol binding protein 4 (RBP4) that distributes vitamin A, as retinol, to peripheral tissues; and (3) it harbors the largest body supply of vitamin A, mostly as retinyl esters, in hepatic stellate cells (HSCs). In times of inadequate dietary intake, the liver maintains stable circulating retinol levels of approximately 2 μmol/L, sufficient to provide the body with this vitamin for months. Liver diseases, in particular those leading to fibrosis and cirrhosis, are associated with impaired vitamin A homeostasis and may lead to vitamin A deficiency. Liver injury triggers HSCs to transdifferentiate to myofibroblasts that produce excessive amounts of extracellular matrix, leading to fibrosis. HSCs lose the retinyl ester stores in this process, ultimately leading to vitamin A deficiency. Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and is a spectrum of conditions ranging from benign hepatic steatosis to non-alcoholic steatohepatitis (NASH); it may progress to cirrhosis and liver cancer. NASH is projected to be the main cause of liver failure in the near future. Retinoic acids are key regulators of glucose and lipid metabolism in the liver and adipose tissue, but it is unknown whether impaired vitamin A homeostasis contributes to or suppresses the development of NAFLD. A genetic variant of patatin-like phospholipase domain-containing 3 (PNPLA3-I148M) is the most prominent heritable factor associated with NAFLD. Interestingly, PNPLA3 harbors retinyl ester hydrolase activity and PNPLA3-I148M is associated with low serum retinol level, but enhanced retinyl esters in the liver of NAFLD patients. Low circulating retinol in NAFLD may therefore not reflect true “vitamin A deficiency”, but rather disturbed vitamin A metabolism. Here, we summarize current knowledge about vitamin A metabolism in NAFLD and its putative role in the progression of liver disease, as well as the therapeutic potential of vitamin A metabolites.

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APOC3 rs2070666 Is Associated with the Hepatic Steatosis Independently of PNPLA3 rs738409 in Chinese Han Patients with Nonalcoholic Fatty Liver Diseases

Abstract: The APOC3 rs2070666 A allele is a risk factor for NAFLD independent of obesity, dyslipidemia, and PNPLA3 rs738409, and it might contribute to increased liver fat content in Chinese Han population.

Cited by 21 publications

References 40 publications

Cholesteryl Ester Transfer Protein Variant (RS1800777) with Liver Histology in Non-Alcoholic Fatty Liver Disease Patients

Cholesteryl Ester Transfer Protein Variant (RS1800777) with Liver Histology in Non-Alcoholic Fatty Liver Disease Patients

Guidelines of prevention and treatment of nonalcoholic fatty liver disease (2018, China)

Disturbed Vitamin A Metabolism in Non-Alcoholic Fatty Liver Disease (NAFLD)

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