Department of Laboratory Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang Province, China.
Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325006, Zhejiang Province, China.
World J Gastroenterol. 2020 Nov 7;26(41):6378-6390. doi: 10.3748/wjg.v26.i41.6378.
The expression of macrophage inhibitory factor-1 (MIC-1) is increased in peripheral blood of patients with chronic hepatitis and liver cirrhosis. However, whether gene polymorphism is correlated with relevant diseases is not yet reported.
To explore the correlation between gene polymorphism in 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 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 ( < 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 ( < 0.05), whereas negatively correlated with total protein and albumin ( < 0.05). The genotype and allele frequency distribution at the rs1059519 locus differed between the two groups ( < 0.05). The allele frequency maintained significant difference after Bonferroni correction ( < 0.05). Logistic multiple regression showed that AST, PIIINP, MIC-1, and genotype GG at the rs1059519 locus were independent relevant factors of CHC ( < 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 ( < 0.05). Meanwhile, we found the MIC-1 level trend to increase among rs1059519 genotypes ( = 0.006) and the level of MIC-1 in GG genotype to be significantly higher than CC genotype ( = 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 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.
巨噬细胞抑制因子-1（MIC-1）在外周血慢性肝炎和肝硬化患者中表达增加。然而，基因多态性是否与相关疾病相关尚未报道。
探讨 基因外显子区基因多态性与慢性丙型肝炎病毒（HCV）感染的关系。
本病例对照研究纳入了 178 例慢性丙型肝炎（CHC）患者作为病例组，同时纳入了来自同一地区的 82 例经筛选检查的健康受试者作为对照组。采用 DNA 测序检测 基因外显子区 rs1059369 和 rs1059519 位点的基因型。同时检测 MIC-1 水平、肝功能指标、肝纤维化指标和 HCV RNA 载量。采用单因素分析比较两组间各参数的差异和相关性。采用多元 logistic 回归分析 CHC 的独立相关因素。
CHC 组患者血浆 MIC-1 水平高于对照组（<0.05），且与丙氨酸氨基转移酶、天冬氨酸氨基转移酶（AST）、III 型前胶原 N 端肽（PIIINP）、IV 型胶原和 HCV RNA 呈显著正相关（<0.05），与总蛋白和白蛋白呈显著负相关（<0.05）。两组 rs1059519 位点的基因型和等位基因频率分布不同（<0.05）。经 Bonferroni 校正后，等位基因频率仍保持显著差异（<0.05）。多因素 logistic 回归显示，AST、PIIINP、MIC-1 和 rs1059519 位点的 GG 基因型是 CHC 的独立相关因素（<0.05）。rs1059369 和 rs1059519 位点之间存在连锁不平衡（LD），CHC 组和对照组之间的 A-C 单倍型分布存在显著差异（<0.05）。同时，我们发现 rs1059519 基因型中 MIC-1 水平呈上升趋势（=0.006），GG 基因型的 MIC-1 水平明显高于 CC 基因型（=0.009，经 Bonferroni 校正）。
CHC 患者血浆 MIC-1 水平升高，与肝细胞损伤、肝纤维化指标和病毒载量相关。 基因 rs1059519 位点多态性与 HCV 感染相关，与血浆 MIC-1 水平相关。G 等位基因和 GG 基因型可能是 CHC 的重要易感因素。
