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

The expression of macrophage inhibitory factor-1 (MIC-1) is increased in peripheral blood of patients with chronic hepatitis and liver cirrhosis. However, whether MIC-1 gene polymorphism is correlated with relevant diseases is not yet reported.


To explore the correlation between gene polymorphism in MIC-1 exon region and chronic hepatitis C virus (HCV) infection.


This case-control study enrolled 178 patients with chronic hepatitis C (CHC) in the case group, and 82 healthy subjects from the same region who had passed the screening examination comprised the control group. The genotypes of rs1059369 and rs1059519 loci in the 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.


The plasma MIC-1 level in the CHC group was higher than that in the control group (P < 0.05), and it was significantly positively correlated with alanine aminotransferase, aspartate aminotransferase (AST), type III procollagen N-terminal peptide (known as PIIINP), type IV collagen, and HCV RNA (P < 0.05), whereas negatively correlated with total protein and albumin (P < 0.05). The genotype and allele frequency distribution at the rs1059519 locus differed between the two groups (P < 0.05). The allele frequency maintained significant difference after Bonferroni correction (Pc < 0.05). Logistic multiple regression showed that AST, PIIINP, MIC-1, and genotype GG at the rs1059519 locus were independent relevant factors of CHC (P < 0.05). Linkage disequilibrium (LD) was found between rs1059369 and rs1059519 loci, and significant difference was detected in the distribution of haplotype A-C between the CHC and control groups (P < 0.05). Meanwhile, we found the MIC-1 level trend to increase among rs1059519 genotypes (P = 0.006) and the level of MIC-1 in GG genotype to be significantly higher than CC genotype (P = 0.009, after Bonferroni correction).


Plasma MIC-1 level was increased in CHC patients and correlated with liver cell damage, liver fibrosis metrics, and viral load. The polymorphism at the MIC-1 gene rs1059519 locus was correlated with HCV infection, and associated with the plasma MIC-1 level. G allele and GG genotype may be an important susceptible factor for CHC.

Keywords: Hepatitis C virus, Chronic infection, Exon region, Polymorphism, Macrophage inhibitory factor-1, Case-control study

Core Tip: In this study, the relationship between the polymorphisms in the exon region of macrophage inhibitory factor-1 (MIC-1), plasma MIC-1 level and chronic hepatitis C virus (commonly known as HCV) infection were preliminarily investigated. We found that the genotype at rs1059519 could influence the plasma MIC-1 level and both were correlated with chronic hepatitis C (CHC), and the G allele at rs1059519 was an independent risk factor for CHC. Therefore, the baseline MIC-1 level of plasma and rs1059519 polymorphisms can be used as a predictive marker for HCV infection.