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CXCL9-11 polymorphisms are associated with liver fibrosis in patients with chronic hepatitis C: a cross-sectional study.

ABSTRACT: BACKGROUND AND AIMS:CXCL9-11 polymorphisms are related to various infectious diseases, including hepatitis C virus (HCV) infection. In this study, we analyzed the association between CXCL9-11 polymorphisms and liver fibrosis in HCV-infected patients. METHODS:We performed a cross-sectional study in 389 patients who were genotyped for CXCL9-11 polymorphisms (CXCL9 rs10336, CXCL10 rs3921, and CXCL11 rs4619915) using the Sequenom's MassARRAY platform. The primary outcome variable was the liver stiffness measurement (LSM). We established three cut-offs of LSM: LSM ? 7.1 kPa (F ? 2-significant fibrosis), LSM ? 9.5 kPa (F ? 3-advanced fibrosis), and LSM ? 12.5 kPa (F4-cirrhosis). RESULTS:Recessive, overdominant and codominant models of inheritance showed significant values, but the overdominant model was the best fitting our data. In this case, CXCL9 rs10336 AG, CXCL10 rs3921 CG and CXCL11 rs4619915 AG were mainly associated with lower values of LSM [(adjusted GMR (aGMR) = 0.85 (p = 0.005), aGMR = 0.84 (p = 0.003), and aGMR = 0.84 (p = 0.003), respectively]. Patients with CXCL9 rs10336 AG genotype had lower odds of significant fibrosis (LSM ? 7.1 kPa) [adjusted OR (aOR) = 0.59 (p = 0.016)], advanced fibrosis (LSM ? 9.5 kPa) [aOR = 0.54 (p = 0.010)], and cirrhosis (LSM ? 12.5 kPa) [aOR = 0.56 (p = 0.043)]. Patients with CXCL10 rs3921 CG or CXCL11 rs4619915 AG genotypes had lower odds of significant fibrosis (LSM ? 7.1 kPa) [adjusted OR (aOR) = 0.56 (p = 0.008)], advanced fibrosis (LSM ? 9.5 kPa) [aOR = 0.55 (p = 0.013)], and cirrhosis (LSM ? 12.5 kPa) [aOR = 0.57 (p = 0.051)]. Additionally, CXCL9-11 polymorphisms were related to lower liver stiffness under a codominant model of inheritance, being the heterozygous genotypes also protective against hepatic fibrosis. In the recessive inheritance model, the CXCL9 rs10336 AA, CXCL10 rs3921 CC and CXCL11 rs4619915 AA were associated with higher LSM values [(adjusted GMR (aGMR) = 1.19 (p = 0.030), aGMR = 1.21 (p = 0.023), and aGMR = 1.21 (p = 0.023), respectively]. Moreover, patients with CXCL9 rs10336 AA genotype had higher odds of significant fibrosis (LSM ? 7.1 kPa) [adjusted OR (aOR) = 1.83 (p = 0.044)] and advanced fibrosis (LSM ? 9.5 kPa) [aOR = 1.85 (p = 0.045)]. Furthermore, patients with CXCL10 rs3921 CC or CXCL11 rs4619915 AA genotypes had higher odds of advanced fibrosis (LSM ? 9.5 kPa) [aOR = 1.89 (p = 0.038)]. CONCLUSIONS:CXCL9-11 polymorphisms were related to likelihood of having liver fibrosis in HCV-infected patients. Our data suggest that CXCL9-11 polymorphisms may play a significant role against the progression of CHC and could help prioritize antiviral therapy.

SUBMITTER: Jimenez-Sousa MA

PROVIDER: S-EPMC5533694 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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CXCL9-11 polymorphisms are associated with liver fibrosis in patients with chronic hepatitis C: a cross-sectional study.

Jiménez-Sousa María Ángeles MÁ Gómez-Moreno Ana Zaida AZ Pineda-Tenor Daniel D Medrano Luz Maria LM Sánchez-Ruano Juan José JJ Fernández-Rodríguez Amanda A Artaza-Varasa Tomas T Saura-Montalban José J Vázquez-Morón Sonia S Ryan Pablo P Resino Salvador S

Clinical and translational medicine 20170728 1

<h4>Background and aims</h4>CXCL9-11 polymorphisms are related to various infectious diseases, including hepatitis C virus (HCV) infection. In this study, we analyzed the association between CXCL9-11 polymorphisms and liver fibrosis in HCV-infected patients.<h4>Methods</h4>We performed a cross-sectional study in 389 patients who were genotyped for CXCL9-11 polymorphisms (CXCL9 rs10336, CXCL10 rs3921, and CXCL11 rs4619915) using the Sequenom's MassARRAY platform. The primary outcome variable was ...[more]

PMID: 28755163

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Project description:BackgroundChronic hepatitis B (CHB) remains a significant global health problem, leading to recurrent inflammation and liver-damaging diseases such as fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Currently, although diagnostic markers for CHB are well established, the indicators for predicting liver injury caused by hepatitis B virus (HBV) infection still need to be further explored. Thus, the identification of credible infectious indicators is urgently needed to facilitate timely clinical intervention and avoid the progression of disease malignancy.MethodsThe Gene Expression Omnibus (GEO) database GSE83148 data set was used to explore the hub genes for HBV infection. The quantitative real-time polymerase chain reaction (qPCR) was used to identify the impact of HBV infection on the expression of hub gene at the cell level. At the same time, serum samples and clinical information were collected from healthy, HBV-free and CHB patients. The enzyme-linked immunosorbent assay (ELISA) was used to verify the results of cell experiments and Pearson correlation analysis was used to clarify hub genes correlation with HBV infection indicators and liver injury-related indicators. Finally, the Gene Expression Profiling Interactive Analysis (GEPIA) database was used to analyze the differences in the expression of hub gene in liver injury diseases.ResultsChemokine (C-X-C motif) ligand (CXCL)8, CXCL9, CXCL10, and CXCL11 were identified as hub genes in HBV infection. After HBV infection, the expression of the four chemokines was significantly increased and the concentrations secreted into serum were also increased. Moreover, the four chemokines were significantly correlated with HBV infection-related indicators and liver injury-related indicators, which were positively correlated with alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hepatitis B e antigen (HBeAg), and negatively correlated with AST/ALT ratio and hepatitis B core antibody (HBcAb). In addition, the expression of CXCL9, CXCL10, and CXCL11 in HCC tissues was significantly higher than in normal tissues.ConclusionUsing a combination of bioinformatics, cell experiments, and clinical correlation analysis, this study showed that CXCL8, CXCL9, CXCL10, and CXCL11 can be used as serum biomarkers to forecast liver injury caused by HBV infection.

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Dataset Information

CXCL9-11 polymorphisms are associated with liver fibrosis in patients with chronic hepatitis C: a cross-sectional study.

Publications

CXCL9-11 polymorphisms are associated with liver fibrosis in patients with chronic hepatitis C: a cross-sectional study.

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