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. 2016 Apr 14;11(4):e0153497.
doi: 10.1371/journal.pone.0153497. eCollection 2016.

Association of Circulating Serum miR-34a and miR-122 with Dyslipidemia among Patients with Non-Alcoholic Fatty Liver Disease

Noel C Salvoza  1 , David C Klinzing  1 , Juliet Gopez-Cervantes  2 , Michael O Baclig  1
Affiliations

Association of Circulating Serum miR-34a and miR-122 with Dyslipidemia among Patients with Non-Alcoholic Fatty Liver Disease

Noel C Salvoza et al. PLoS One. .

Abstract

Non-alcoholic fatty liver disease (NAFLD) covers a spectrum of diseases from simple steatosis to non-alcoholic steatohepatitis, with approximately 20% risk of progressing to fibrosis and cirrhosis. The aim of this study was to compare the relative expression levels of circulating miR-21, miR-34a, miR-122, miR-125b and miR-375 between healthy controls and NAFLD patients, and to assess the feasibility of microRNAs as potential biomarkers for NAFLD. A cross-sectional study was conducted to evaluate circulating serum miRNAs as potential diagnostic markers for NAFLD. Twenty-eight clinically diagnosed and histologically-confirmed NAFLD patients, as well as 36 healthy controls were enrolled in this study. The relative expression of serum microRNAs were calculated using the comparative cycle threshold with spiked-in C. elegans miR-39 as exogenous internal control. Serum levels of miR-34a and miR-122 were significantly higher in NAFLD patients than in healthy controls (P = <0.0001). Positive correlations were observed between serum miR-34a with very low density lipoprotein cholesterol (VLDL-C) and triglyceride levels. However, the expression levels of miR-34a and miR-122 did not correlate with the histological features of NAFLD. Interestingly, receiver operating characteristic (ROC) curve analysis revealed that miR-34a and miR-122 are potential markers for discriminating NAFLD patients from healthy controls with an area under the curve (AUC) values of 0.781 and 0.858, respectively. Serum levels of miR-34a and miR-122 were found to be significantly higher among NAFLD patients, and were positively correlated with VLDL-C and triglyceride levels. Thus, circulating miR-34a and miR-122 can be used as potential biomarkers for discriminating NAFLD patients from healthy controls. Larger cohorts are required to validate the utility of miR-34a and miR-122 in monitoring liver injury.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Up-regulation of serum miR-34a and miR-122 in NAFLD patients.
Serum expression levels of miR-34a and miR-122 were measured in healthy controls and NAFLD patients. The relative expression levels were normalized to synthetic spike-in C. elegans miR-39. The P value was calculated according to Mann-Whitney U test. The horizontal lines indicate the medians.
Fig 2
Fig 2. Relative expression of serum miR-34a and miR-122 among healthy controls and NAFLD patients at various degree of liver steatosis.
The P values were calculated according to Kruskal-Wallis test with Dunn’s multiple comparison post-test. In the boxplots, the vertical lines indicate the range and the horizontal boundaries of the boxes represent the first and third quartile. The lines inside the boxes denote the medians. * p>0.01–0.05; ** p = 0.001–0.01; *** p<0.001.
Fig 3
Fig 3. Relative expression of serum miR-34a and miR-122 among healthy controls and NAFLD patients according to stage of fibrosis and combined stages of fibrosis.
The P values were calculated according to Kruskal-Wallis test with Dunn’s multiple comparison post-test. In the boxplots, the vertical lines indicate the range and the horizontal boundaries of the boxes represent the first and third quartile. The lines inside the boxes denote the medians. * p>0.01–0.05; ** p = 0.001–0.01; *** p<0.001.
Fig 4
Fig 4. Relative expression of serum miR-34a and miR-122 among healthy controls and NAFLD patients at various degree of inflammation.
The P values were calculated according to Kruskal-Wallis test with Dunn’s multiple comparison post-test. In the boxplots, the vertical lines indicate the range and the horizontal boundaries of the boxes represent the first and third quartile. The lines inside the boxes denote the medians. * p>0.01–0.05; ** p = 0.001–0.01; *** p<0.001.
Fig 5
Fig 5. ROC curve analysis for serum miR-34a, miR-122 and ALT.
The AUC for serum miR-34a, miR-122 and ALT are 0.781, 0.858 and 0.832, respectively.
See this image and copyright information in PMC

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