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Association between IL7R polymorphisms and severe liver disease in HIV/HCV coinfected patients: a cross-sectional study.

ABSTRACT: Interleukin-7 (IL-7) is a critical factor for T cell development and for maintaining and restoring homeostasis of mature T cells. Polymorphisms at ?-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.We 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.Patients 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).The 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.

SUBMITTER: Guzman-Fulgencio M

PROVIDER: S-EPMC4487067 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Association between IL7R polymorphisms and severe liver disease in HIV/HCV coinfected patients: a cross-sectional study.

Guzmán-Fulgencio María M Berenguer Juan J Jiménez-Sousa María A MA Pineda-Tenor Daniel D Aldámiz-Echevarria Teresa T García-Broncano Pilar P Carrero Ana A García-Álvarez Mónica M Tejerina Francisco F Diez Cristina C Vazquez-Morón Sonia S Resino Salvador S

Journal of translational medicine 20150630

<h4>Background</h4>Interleukin-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.<h4>Methods</h4>We p ...[more]

PMID: 26123260

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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: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: Peroxisome proliferator-activated receptor gamma-2 gene (PPAR?2) rs1801282 (Pro12Ala) polymorphism has been associated with lower risk of metabolic disturbance and atherosclerosis. The aim of this study was to analyze the association between the Pro12Ala polymorphism and cardiometabolic risk factors in human immunodeficiency virus (HIV)/Hepatitis C virus (HCV)-coinfected patients. METHODS: We carried out a cross-sectional study on 257 HIV/HCV coinfected patients. PPAR?2 polymorphism was genotyped by GoldenGate® assay. The main outcome measures were: i) serum lipids (cholesterol, triglycerides, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), LDL-C/HDL-C, and atherogenic index (AI)); ii) homeostatic model assessment (HOMA-IR) values; iii) serum adipokines (leptin, adiponectin, resistin, plasminogen activator inhibitor-1(PAI-1), hepatic growth factor (HGF), and nerve growth factor (NGF)). Generalized Linear Models (GLM) with gamma distribution (log-link) were used to investigate the association between PPAR?2 polymorphism and continuous outcome variables. This test gives the differences between groups and the arithmetic mean ratio (AMR) in continuous outcome variables between groups. RESULTS: The rs1801282 CG/GG genotype was associated with low values of cholesterol (adjusted arithmetic mean ratio (aAMR)?=?0.87 (95% of confidence interval (95% CI)?=?0.79; 0.96); p?=?0.004) and LDL-C (aAMR?=?0.79 (95% CI?=?0.68; 0.93); p?=?0.004). Furthermore, rs1801282 CG/GG was associated with low values of HOMA-IR (aAMR?=?0.69 (95% CI?=?0.49; 0.98); p?=?0.038) among patients with significant liver fibrosis (F???2). Moreover, rs1801282 CG/GG was also associated with low serum values of hepatic growth factor (HGF) (aAMR?=?0.61 (95% CI?=?0.39; 0.94); p?=?0.028), and nerve growth factor (NGF) (aAMR?=?0.47 (95% CI?=?0.26; 0.84); p?=?0.010). The serum levels of leptin, adiponectin, resistin, and PAI-1 did not show significant differences. CONCLUSIONS: The presence of PPAR?2 rs1801282 G allele (Ala variant) was associated with a protective cardiometabolic risk profile versus CC genotype in HIV/HCV-coinfected patients. Thus, PPAR?2 rs1801282 polymorphism may play a significant role in the development of metabolic disorders in HIV/HCV coinfected patients, and might have an influence on the cardiovascular risk.

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Association between IL7R polymorphisms and severe liver disease in HIV/HCV coinfected patients: a cross-sectional study.

Publications

Association between IL7R polymorphisms and severe liver disease in HIV/HCV coinfected patients: a cross-sectional study.

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