Case Control Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 7, 2020; 26(41): 6378-6390
Published online Nov 7, 2020. doi: 10.3748/wjg.v26.i41.6378
Associations of content and gene polymorphism of macrophage inhibitory factor-1 and chronic hepatitis C virus infection
Xun-Jun Yang, Xiao-Ou Wang, Yao Chen, Song-Dao Ye
Xun-Jun Yang, Xiao-Ou Wang, Song-Dao Ye, Department of Laboratory Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang Province, China
Yao Chen, Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325006, Zhejiang Province, China
Author contributions: Yang XJ and Wang XO carried out the study, participated in data collection, and drafted the manuscript; Chen Y provided advice for this research and took part in the manuscript revision; Ye SD conceived the study and revised the manuscript; All authors read and approved the final manuscript.
Supported by the Medical and Health Research Science and Technology Plan Project of Zhejiang Province, No. 2016KYB191.
Institutional review board statement: This study was approved by the Ethics Committee of The Second Affiliated Hospital of Wenzhou Medical University (LCKY2016-150).
Informed consent statement: All patients signed the informed consent before participation in the study.
Conflict-of-interest statement: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Data sharing statement: The data that support the findings of this study are available from The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Song-Dao Ye, MSc, Doctor, Department of Laboratory Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, No. 109 Xueyuan West Road, Puxie Street, Lucheng District, Wenzhou 325027, Zhejiang Province, China.
Received: June 18, 2020
Peer-review started: June 18, 2020
First decision: August 22, 2020
Revised: September 7, 2020
Accepted: September 29, 2020
Article in press: September 29, 2020
Published online: November 7, 2020
Research background

Macrophage inhibitory factor-1 (MIC-1), regulating the inflammatory response and apoptosis pathway, is involved in multiple organ damage and the progress of various diseases. In recent years, scholars have found that the MIC-1 expression is increased in chronic viral hepatitis, liver cirrhosis, and small cell liver cancer patients. However, the correlation between MIC-1 gene polymorphism and hepatitis C virus (HCV) infection and treatment has not been reported.

Research motivation

To investigate whether plasma MIC-1 level is correlated with liver cell injury, liver fibrosis index and viral load in chronic hepatitis C (CHC) patients. To investigate the relationship between the polymorphism of rs1059369 and rs1059519 in the MIC-1 exon region and the expression level of MIC-1 in plasma and the susceptibility to CHC.

Research objectives

The study aimed to explore the correlation between MIC-1 and the chronic infection of HCV by determining the expression level of MIC-1 and the gene polymorphism in the exon region in CHC patients and healthy subjects who cleared the screening examination. These findings will provide a basis for the diagnosis and treatment of such diseases.

Research methods

This case-control study enrolled 178 patients with CHC and 82 healthy subjects. The genotypes of rs1059369 and rs1059519 loci in MIC-1 gene exon were detected by DNA sequencing. Also, the MIC-1 level, liver function metrics, liver fibrosis metrics, and HCV RNA load were determined. Univariate analysis was used to compare the differences and correlations between the two groups with respect to these parameters. Multivariate logistic regression was used to analyze the independent relevant factors of CHC.

Research results

Compared with healthy subjects, CHC patients had higher plasma levels of MIC-1 and alanine aminotransferase (ALT), aspartate aminotransferase (AST), type III procollagen N-terminal peptide (PIIINP), type IV collagen (CIV), HCV RNA, and lower levels of total protein and albumin. The genotype and allele frequency distribution of rs1059519 were significantly different between CHC group and control group. Logistic multivariate regression revealed that AST (ALT), PIIINP (CIV), the MIC-1 level, rs1059519 GG genotype related to CHC, are independent risk factors. There were statistically significant differences in plasma MIC-1 level between different rs1059519 genotypes (P = 0.006), and GG genotype was significantly higher than CC genotype (P = 0.009).

Research conclusions

The plasma MIC-1 level in CHC patients is correlated with liver cell damage, liver fibrosis, and viral load. The polymorphism of MIC-1 gene at rs1059519 locus affects plasma MIC-1 level and is associated with HCV infection.

Research perspectives

As the number of spontaneous viral clearance (SVC) was far less than 20% among the CHC cases that we have collected and did not meet the statistical requirements, we had to exclude this group in this study for the time being. However, we will continue to collect more cases in the future, and add the SVC group to further study the relationship between MIC-1 and SVC. In addition, the correlation between MIC-1 and antiviral efficacy and prognosis of CHC is also worth further exploration.