scholarly journals APOC3 rs2070667 Associates with Serum Triglyceride Profile and Hepatic Inflammation in Nonalcoholic Fatty Liver Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Qing-Yang Xu ◽  
Han Li ◽  
Hai-Xia Cao ◽  
Qin Pan ◽  
Jian-Gao Fan

Single-nucleotide polymorphisms (SNPs) of apolipoprotein C3 (APOC3) play important role in lipid metabolism, and dyslipidemia underlies nonalcoholic fatty liver disease (NAFLD). But the correlation of serum lipidomics, APOC3 SNPs, and NAFLD remains limited understood. Enrolling thirty-four biopsy-proven NAFLD patients from Tianjin, Shanghai, Fujian, we investigated their APOC3 genotype and serum lipid profile by DNA sequencing and ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), respectively. Scoring of hepatocyte steatosis, ballooning, lobular inflammation, and liver fibrosis was then performed to reveal the role of lipidomics-affecting APOC3 SNPs in NAFLD-specific pathological alterations. Here, we reported that APOC3 SNPs (rs4225, rs4520, rs5128, rs2070666, and rs2070667) intimately correlated to serum lipidomics in NAFLD patients. A allele instead of G allele at rs2070667, which dominated the SNPs underlying lipidomic alteration, exhibited downregulatory effect on triacylglycerols (TGs: TG 54 : 7, TG 54 : 8, and TG 56 : 9) containing polyunsaturated fatty acid (PUFA). Moreover, subjects with low-level PUFA-containing TGs were predisposed to high-grade lobular inflammation (TG 54 : 7, rho = − 0.454 and P = 0.007 ; TG 54 : 8, rho = − 0.411 and P =0.016; TG 56 : 9, rho = − 0.481 and P = 0.004 ). The significant correlation of APOC3 rs2070667 and inflammation grading [G/G vs. G/A+A/A: 0.00 (0.00 and 1.00) vs. 1.50 (0.75 and 2.00), P = 0.022 ] further confirmed its pathological action on the basis of lipidomics-impacting activity. These findings suggest an inhibitory effect of A allele at APOC3 rs2070667 on serum levels of PUFA-containing TGs, which are associated with high-grade lobular inflammation in NAFLD patients.

2015 ◽  
Vol 24 (3) ◽  
pp. 293-300 ◽  
Author(s):  
Salih Boga ◽  
Huseyin Alkim ◽  
Canan Alkim ◽  
Ali Riza Koksal ◽  
Mehmet Bayram ◽  
...  

Background & Aims: Mild iron overload is frequently reported in patients with nonalcoholic fatty liver disease (NAFLD). Hepcidin is the master iron-regulatory peptide and hemojuvelin (HJV) is the key regulator of iron-dependent secretion of hepcidin. The aims of this study were to evaluate serum HJV and hepcidin levels in patients with biopsy-proven NAFLD with and without hepatic iron overload, and to identify potential associations of HJV and hepcidin with the clinical characteristics of the patients enrolled. Methods: Serum levels of HJV and hepcidin were measured in 66 NAFLD patients with (n=12) and without (n=54) iron overload, and controls (n=35) by enzyme-linked immunosorbent assay. Hemojuvelin and hepcidin levels were assessed in relation to clinical characteristics and liver histologic evaluation of the participants. Results: Significantly lower serum HJV (281.1 [239.2-353.6] vs. 584.8 [440.3-661] ng/ml, p<0.001) and similar serum hepcidin levels (60.5±31.1 vs. 55.8±11.9 ng/ml, p=0.285) were found in NAFLD patients when compared to controls. İron-overloaded NAFLD patients had significantly lower HJV (249.9 [187.6-296.3] vs. 292.9 [243-435] ng/ml, p=0.032) and significantly higher hepcidin (78.4±35.5 vs. 56.5±28.9ng/ml, p=0.027) levels than NAFLD patients without iron overload. Fibrosis stage was significantly higher in iron overloaded NAFLD group (p<0.001). Ferritin levels correlated significantly both with HOMA-IR (r=0.368, p=0.002) and fibrosis stage (r=0.571, p<0.001). Conclusions: Our findings suggest that HJV levels are low in NAFLD and even lower in iron overloaded NAFLD, while hepcidin levels are higher in NAFLD with iron overload. The gradually decreased HJV and increased hepcidin concentrations in our patients most likely reflect the physiological response to iron accumulation in the liver.


2013 ◽  
Vol 31 (4) ◽  
pp. 523-530 ◽  
Author(s):  
Fábio da Veiga Ued ◽  
Virgínia Resende S. Weffort

OBJECTIVE: To review the literature on the importance of antioxidant vitamins, analyzed in the context of dietary intake, its plasma levels, and its current use as a supplementation treatment in obese children and adolescents with nonalcoholic fatty liver disease. DATA SOURCES: The articles were identified in Lilacs, Ibecs, SciELO, PubMed/Medline, and Scopus databases. To conduct the survey, the "fatty liver" descriptor was associated to the following words: "children", "antioxidants" and "vitamins". The search was limited to articles written in Portuguese, Spanish and English, with publication date until December, 2012. DATA SYNTHESIS: Six studies were selected. The survey revealed a low dietary intake and low antioxidant vitamins serum levels in this population. The changes in lifestyle, with adequate dietary intake of vitamins, and the increase in physical activity were associated with a significant improvement in liver histology and in laboratory tests. Vitamin supplementation also improved the disease progression markers, as the alanine aminotransferase serum levels and the histological characteristics of lobular inflammation and hepatocellular damage. However, these improvements were not statistically significant in all studies. CONCLUSIONS: There is insufficient evidence to recommend or to refute antioxidant supplementation in patients with simple steatosis or steatohepatitis. The changes in lifestyle seem to be, at the present time, the more advisable therapy.


Author(s):  
Gholamreza Rezamand ◽  
Touraj Mahmoudi ◽  
Seidamir Pasha Tabaeian ◽  
Hamid Farahani ◽  
Fatemeh Shahinmehr ◽  
...  

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is an emerging global chronic liver disease worldwide. Considering the powerful association between NAFLD, insulin resistance (IR) and obesity, as well as the key role of ghrelin in these metabolic disorders, we hypothesized that some single nucleotide polymorphisms (SNPs) of the ghrelin (GHRL) and ghrelin receptor (GHSR) genes might be associated with NAFLD. Methods We conducted a case-control retrospective study of 150 cases with biopsy-proven NAFLD and 155 controls. The diagnosis of NAFLD was established before the start of the genotyping process. All the 305 subjects were genotyped for GHRL SNP rs26802 or -501T>G and GHSR SNP rs572169 or Arg159Arg using the PCR-RFLP method. Results The GHRL rs26802 “GG” genotype compared with the “TT” genotype and “TT+TG” genotype appears to be a marker of decreased NAFLD susceptibility even after adjustment for confounding factors (P = 0.006; OR = 0.14, 95% CI = 0.03–0.56 and P = 0.003; OR = 0.16, 95% CI = 0.05–0.53, respectively). However, we observed no significant difference in genotype or allele frequencies between the cases and controls for GHSR SNP rs572169. Conclusions These findings proposed, for the first time, that the GHRL rs26802 “GG” genotype has a protective effect against NAFLD. Nonetheless, this observation warrants further investigations in other populations.


2020 ◽  
Vol 158 (6) ◽  
pp. S-1408
Author(s):  
Hani Shamseddeen ◽  
Vijay Are ◽  
Emily Smith ◽  
Tiebing Liang ◽  
Samer Gawrieh ◽  
...  

2011 ◽  
Vol 9 (4) ◽  
pp. 287-290 ◽  
Author(s):  
Ebubekir Senates ◽  
Yusuf Yilmaz ◽  
Yasar Colak ◽  
Oguzhan Ozturk ◽  
Mustafa Erhan Altunoz ◽  
...  

2012 ◽  
Vol 47 (12) ◽  
pp. 1488-1493 ◽  
Author(s):  
Yusuf Yilmaz ◽  
Fatih Eren ◽  
Yasar Colak ◽  
Ebubekir Senates ◽  
Cigdem Ataizi Celikel ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Juliana Maya Monteiro ◽  
Geysa Maya Monteiro ◽  
Adriana Caroli-Bottino ◽  
Vera Lucia Pannain

The morphological features of nonalcoholic fatty liver disease (NAFLD) range from steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. Liver biopsy remains the main tool for NASH diagnosis and many histological systems to diagnose and grade NAFLD were proposed. We evaluated the relationship among NAFLD activity score (NAS), histological diagnoses (non-NASH, possible NASH, and definite NASH), and histological algorithm proposed by Bedossa et al.; additionally the degrees of morphological features were semiquantified and correlated with non-NASH and NASH. Seventy-one liver biopsies were studied. The agreement among the three systems considering NASH and non-NASH was excellent (Κ=0.96). Among the 22 biopsies with NAS 3-4, 72.7% showed to be NASH according to Bedossa’s algorithm. The degree of steatosis, ballooning, lobular inflammation, and fibrosis stage were correlated with NASH (P<0.001). Fibrosis stage 1 was also found in non-NASH. Over the spectrum of NAFLD, no association was observed between intensity of steatosis and fibrosis grade. The degrees of lobular inflammation showed association with fibrosis stage (P<0.0001). In conclusion, there is agreement among different NAFLD classifications and NAS > 4 may be a better cutoff from which to consider NASH diagnosis; besides the highest degrees of steatosis, ballooning, inflammation, and fibrosis are associated with NASH.


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