Associations of content and gene polymorphism of macrophage inhibitory factor-1 and chronic hepatitis C virus infection

Abstract

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

GDF-15: A Potential Biomarker and Therapeutic Target in Systemic Lupus Erythematosus

“…G to C mutation suggested higher risk of SLE, which may lead to increased GDF-15 mRNA expression, and increased serum levels of GDF-15 in SLE patients. Rs1059519 was located at exon, which has been reported to associate with GDF-15 expression and relate to chronic hepatitis C infection, left ventricular hypertrophy (20)(21)(22). In our study, rs1059519 polymorphism was related to SLE risk and SLE complicated with discoid and pleurisy, suggesting that rs1059519 may regulate vascular injury and inflammation.…”

Correlations between growth differentiation factor 15 (GDF-15) serum levels and gene polymorphism with type 2 diabetes mellitus

“…In this study, we also found that in the dominant model, people carrying rs1059519 C allele had lower FPG levels, indicating that people carrying G allele were more likely to have elevated FPG and HbA1c levels. Previous study has shown that the polymorphism of rs1059519 was correlated with the level of plasma MIC-1 (GDF-15), and the level of MIC-1 in GG genotype was significantly higher than that in CC genotype [ 30 ]. A study of hypertensive patients in China found that rs1059519 G allele have significantly increased plasma levels of GDF-15 [ 31 ].…”

Association of macrophage inhibitory factor -1 polymorphisms with antiviral efficacy of type 1b chronic hepatitis C

“…Our previous study found the genotype and allele frequency distribution at the rs1059519 locus, not for rs1059369, significant differed between the patients and healthy controls. The genotype GG at the rs1059519 locus follow with high content of AST, PIIINP, MIC-1 were suggested as independent relevant factors for CHC [ 40 ]. In the current study, the genotype and allele frequency of the two sites did not differ significantly between the responsive and non-responsive groups and between the SVR and non-SVR groups ( P > 0.05).…”