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ADAR1 polymorphisms are related to severity of liver fibrosis in HIV/HCV-coinfected patients.

ABSTRACT: The adenosine deaminase acting on RNA (ADAR1) gene is an interferon-stimulated gene involved in liver injury protection. Our aim was to analyze the association of polymorphisms within this gene with the severity of liver disease in European HIV/HCV-coinfected patients. We performed a cross-sectional study in 220 patients that underwent a liver biopsy. Five SNPs in the ADAR1 gene (rs1127326, rs1127317, rs1127314, rs1127313, rs2229857) were genotyped by GoldenGate assay. The outcome variables were fibrosis stage and necroinflammatory activity grade by METAVIR-score, aspartate aminotransferase to platelet ratio index (APRI), FIB-4 index, and fibrosis progression rate (FPR). In multivariate analysis, fibrosis progression rate (FPR) (aAMRs?=?0.97) decreased in a dose-dependent manner with the presence of rs2229857_T, rs1127313_G, rs1127314_G and rs1127317_G; while rs1127326_T allele had only significant associations with FIB-4 (aAMRs???0.63) and FPR (aAMRs???0.97). Moreover, carriers of rs2229857_T, rs1127314_G, rs1127317_G, and rs1127326_T alleles were protected against advanced fibrosis (F???3) (adjusted ORs (aORs)???0.44), APRI???1.5 (aORs???0.33), and FPR???0.075 (aORs???0.45). rs1127313_G carriers showed lower odds of having F???3 (aORs?=?0.39), FIB4???3.25 (aOR?=?0.22) and FPR???0.075 (aORs?=?0.44). In conclusion, ADAR1 polymorphisms protected against severe liver disease in HIV/HCV-coinfected patients. These results could be used to improve therapeutic decision-making in clinical practice.

SUBMITTER: Medrano LM

PROVIDER: S-EPMC5635123 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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ADAR1 polymorphisms are related to severity of liver fibrosis in HIV/HCV-coinfected patients.

Medrano Luz M LM Berenguer Juan J Jiménez-Sousa María A MA Aldámiz-Echevarria Teresa T Tejerina Francisco F Diez Cristina C Vigón Lorena L Fernández-Rodríguez Amanda A Resino Salvador S

Scientific reports 20171010 1

The adenosine deaminase acting on RNA (ADAR1) gene is an interferon-stimulated gene involved in liver injury protection. Our aim was to analyze the association of polymorphisms within this gene with the severity of liver disease in European HIV/HCV-coinfected patients. We performed a cross-sectional study in 220 patients that underwent a liver biopsy. Five SNPs in the ADAR1 gene (rs1127326, rs1127317, rs1127314, rs1127313, rs2229857) were genotyped by GoldenGate assay. The outcome variables were ...[more]

PMID: 29018269

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Project description:HIV and HCV coinfection leads to accelerated liver fibrosis, in which microbial translocation and systemic inflammation might play important roles. This study aimed to provide an extensive profile of the plasma microbial translocation and inflammation biomarkers associated with advanced liver fibrosis among HIV-HCV-coinfected patients. This cross-sectional study recruited 343 HIV-HCV-coinfected patients on combination antiretroviral therapy (cART) from a rural prefecture of Yunnan province in Southwest China. The plasma concentrations of sCD14 and 27 cytokines and chemokines were assayed and compared against advanced or mild levels of liver fibrosis. Of the 343 HIV-HCV-coinfected patients, 188 (54.8%) had severe or advanced liver fibrosis (FIB-4 > 3.25). The patients with advanced liver fibrosis (FIB-4 > 3.25 vs. FIB-4 ≤ 3.25) had higher plasma levels of interleukin (IL)-1β, IL-6, IL-7, IL-9, IL-12, IL-15, IL-17, granulocyte macrophage colony stimulating factor (GM-CSF), Interferon-γ (IFN-γ), tumor necrosis factor (TNF-α), IL-4, IL-10, IL-13, fibroblast growth factor 2 (FGF-basic), and Monocyte chemoattractant protein-1 (MCP-1). Multivariable logistic regression models showed that advanced liver fibrosis was associated with an increased plasma level of IL-1β, IL-6, IL-7, IL-12, IL-17, GM-CSF, IFN-γ, IL-4, IL-10, MCP-1, Eotaxin, and FGF-basic, with FGF-basic continuing to be positively and significantly associated with advanced liver fibrosis, after Bonferroni correction for multiple comparisons (adjusted odds ratio (aOR) = 1.92; 95%CI: 1.32-2.81; p = 0.001). Plasma sCD14 was also significantly associated with advanced liver fibrosis (aOR = 1.13; 95%CI: 1.01-1.30; p = 0.049). HIV-HCV-coinfected patients are living with a high prevalence of advanced liver fibrosis which coexists with a mixture of elevated plasma inflammation and microbial translocation biomarkers. The significant associations of advanced liver fibrosis with FGF-basic and sCD14 may reveal pathogenic mechanisms and potential clinical intervention targets for liver fibrosis in HCV-HIV coinfection.

Project description:Background and aimsTRIM5 and TRIM22 are restriction factors involved in innate immune response and exhibit anti-viral activity. Single nucleotide polymorphisms (SNPs) at TRIM5 and TRIM22 genes have shown to influence several viral infections such as human immunodeficiency virus (HIV), hepatitis B, as well as measles and rubella vaccination. The aim of this study is to analyze whether TRIM5 and TRIM22 polymorphisms are associated with liver fibrosis inflammation-related biomarkers and response to pegylated-interferon-alpha plus ribavirin (pegIFNα/RBV) therapy in HIV/hepatitis C virus (HCV) coinfected patients.MethodsA retrospective study was performed in 319 patients who started pegIFNα/RBV therapy. Liver fibrosis stage was characterized in 288 patients. TRIM5 rs3824949 and TRIM22 polymorphisms (rs1063303, rs7935564, and rs7113258) were genotyped using the GoldenGate assay. The primary outcomes were: a) significant liver fibrosis (≥F2) evaluated by liver biopsy or transient elastography (liver stiffness values ≥7.1 Kpa); b) sustained virological response (SVR) defined as no detectable HCV viral load (<10 IU/mL) at week 24 after the end of the treatment. The secondary outcome variable was plasma chemokine levels.ResultsPatients with TRIM5 rs3824949 GG genotype had higher SVR rate than patients with TRIM5 rs3824949 CC/CG genotypes (p = 0.013), and they had increased odds of achieving SVR (adjusted odds ratio (aOR = 2.58; p = 0.012). Patients with TRIM22 rs1063303 GG genotype had higher proportion of significant liver fibrosis than patients with rs1063303 CC/CG genotypes (p = 0.021), and they had increased odds of having significant hepatic fibrosis (aOR = 2.19; p = 0.034). Patients with TRIM22 rs7113258 AT/AA genotype had higher SVR rate than patients with rs7113258 TT genotypes (p = 0.013), and they had increased odds of achieving SVR (aOR = 1.88; p = 0.041). The TRIM22 haplotype conformed by rs1063303_C and rs7113258_A was more frequent in patients with SVR (p = 0.018) and was significantly associated with achieving SVR (aOR = 2.80; p = 0.013). The TRIM5 rs3824949 GG genotype was significantly associated with higher levels of GRO-α (adjusted arithmetic mean ratio ((aAMR) = 1.40; p = 0.011) and MCP-1 (aAMR = 1.61; p = 0.003).ConclusionsTRIM5 and TRIM22 SNPs are associated to increased odds of significant liver fibrosis and SVR after pegIFNα/RBV therapy in HIV/HCV coinfected patients. Besides, TRIM5 SNP was associated to higher baseline levels of circulating biomarkers GRO and MCP-1.

Project description:BackgroundInterleukin-7 (IL-7) is a critical factor for T cell development and for maintaining and restoring homeostasis of mature T cells. Polymorphisms at α-chain of the IL-7 receptor (IL7R or CD127) gene are related to evolution of HIV-infection, but there are no data concerning the evolution of hepatitis C virus (HCV) infection. The aim of this study was to analyze the association between IL7R polymorphisms and severe liver disease in HCV/HIV coinfected patients.MethodsWe performed a cross-sectional study in 220 naïve patients who underwent a liver biopsy. IL7R polymorphisms (rs6897932, rs987106 and rs3194051) were genotyped using the GoldenGate(®) assay. The outcome variables were: (a) liver biopsy: advanced fibrosis (F ≥ 3), severe activity grade (A3); (b) non-invasive indexes: advanced fibrosis (APRI ≥1.5 and FIB-4 ≥3.25). Logistic regression analysis was used to investigate the association between IL7R polymorphisms and outcome variables. This test gives the differences between groups and the odds ratio (OR) for liver disease.ResultsPatients with rs6897932 CC genotype had higher likelihood of having A3 than patients with rs6897932 CT/TT (adjusted odds ratio (aOR) = 4.16; p = 0.026). Patients with rs987106 TT genotype had higher odds of having F ≥ 3 (aOR = 3.09; p = 0.009) than rs987106 AA/AT carriers. Finally, patients with rs3194051 AA genotype had higher odds of having severe liver fibrosis (F ≥ 3; APRI ≥1.5, and FIB4 ≥3.25) than patients with rs3194051 AG/GG genotype [aOR = 2.73 (p = 0.010); aOR = 2.52 (p = 0.029); and aOR = 4.01 (p = 0.027); respectively]. The CTA haplotype (comprised of rs6897932, rs987106, and rs3194051) carriers had higher odds of having F ≥ 3 (aOR = 1.85; p = 0.012), APRI ≥1.5 (aOR = 1.94; p = 0.023), and FIB4 ≥3.25 (aOR = 2.47; p = 0.024). Conversely, the CAG haplotype carriers had lower odds of having F ≥ 3 (aOR = 0.48; p = 0.011), APRI ≥1.5 (aOR = 0.48; p = 0.029), and FIB4 ≥3.25 (aOR = 0.29; p = 0.010).ConclusionsThe presence of IL7R polymorphisms seems to be related to severe liver disease in HIV/HCV coinfected patients, because patients with unfavorable IL7R genotypes (rs6897932 CC, rs987106 TT, and rs3194051AA) had a worse prognosis of CHC.

Dataset Information

ADAR1 polymorphisms are related to severity of liver fibrosis in HIV/HCV-coinfected patients.

Publications

ADAR1 polymorphisms are related to severity of liver fibrosis in HIV/HCV-coinfected patients.

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