IL28B Polymorphisms Rs12979860 Research Articles

Association between IL28B Polymorphisms and Outcomes of Hepatitis B Virus Infection: A meta-analysis

BackgroundInterleukin (IL) 28B polymorphisms encoding pro-inflammatory and anti-inflammatory cytokines trigger diverse clinical outcome of hepatitis virus infection. However, there is controversy concerning the association of IL28B polymorphisms with the outcome of hepatitis B virus (HBV) infection, with several studies obtaining inconsistent results. We performed a meta-analysis to evaluate the role of 3 single nucleotide polymorphisms (SNPs) rs12979860, rs12980275 and rs8099917 in the progression of HBV infection, overall and by ethnicity.MethodsSearched PubMed, Embase and Wiley Online Library electronic databases using ‘interleukin 28B’, ‘IL 28B’, ‘IL 28B polymorphism’, ‘hepatitis B virus’, ‘HBV’, and performed meta- analysis for rs12979860, rs12980275 and rs8099917 in Asian and Caucasian populations under the dominant recessive and allele model.ResultsEighteen studies were found in total and used for this meta-analysis, including 5587 cases and 4295 controls. The IL28B polymorphism rs12979860 had no association with HBV persistence (CC vs CT + TT: OR = 0.86, 95% CI = 0.76–1.00; TT vs CT + CC: OR = 1.14, 95% CI = 0.76–1.70; T vs C: OR = 1.03, 95% CI = 0.94–1.13). Similarly, neither rs12980275 nor rs8099917 had associations with HBV persistence (rs12980275 in AA vs AG + AA: OR = 1.15, 95% CI = 0.96–1.38; rs8099917 in TT vs GT + GG: OR = 1.15, 95% CI = 0.96–1.39). There was also no significant association of IL28B polymorphisms with persistent HBV infection in Asians or Chinese. There was no evidence of an association of rs12979860 with the HBV-related hepatocellular carcinoma susceptibility (T vs C: OR = 1.53, 95% CI = 0.96–2.43).ConclusionIL28B polymorphisms had no association with the outcome of HBV infection overall, nor in the Asians and the Chinese. These 3 SNPs might not be relevant to the development of HBV infection.

ROLE OF SERUM INTERLEUKIN – 10 AND INTERLEUKIN -28B GENE POLYMORPHISMS IN PREDICTING TREATMENT RESPONSE OF HEPATITIS C PATIENTS

Background: Hepatitis C virus infection (HCV) is a global health problem which develops chronic hepatic diseases including liver cirrhosis and hepatocellular carcinoma. IL28B polymorphisms rs12979860 CC genotype and low serum level of interleukin10 were associated to protect the patients of HCV infection and rapid virological response (RVR) in HCV patients treated for four weeks with pegIFNα/ribavirin (IFNα/RIB). Subjects and methods: The study was carried out on 49 Egyptian HCV patients, Patients with other types of viral hepatitis, unfavourable haematological picture & decompensated liver function including cirrhosis and Autoimmune hepatitis were excluded. Patients who responsing to IFNα/RIB after four weeks were classified as RVR (n = 18) and Non-RVR (n = 31). IL28B polymorphisms at rs12979860, the resulting genotypes are CC, CT or TT, and Serum IL10 was measured by standard sandwich enzyme-linked immune-sorbent assay technology for both groups. Results: Il28B CC genotype was 67.4 % in responder group (RVR) 38.7% in non-responder group (non RVR) (p= 0.01), CC genotype with serum IL10 80 pg/mL (p= 0.00). Conclusion: the relationship of genotype CC of IL28B at rs12979869 and the effect of IFNα/RIB to maintain the serum level of IL10 decrease and to achieve better chances to cure the HCV patients from the virus.

THE PATHOGENETIC SIGNIFICANCE OF GENE IL28B POLYMORPHISMS AT SITES RS12979860 AND RS8099917 IN THE DEVELOPMENT OF CHRONIC VIRAL HEPATITIS C IN PATIENTS OF THE SOUTH-EASTERN REGION OF BELARUS

To study the role of IL28B gene polymorphisms in the development of chronic hepatitis C, we have determined polymorphic types of the gene at sites rs12979860 and rs8099917 using allele-specific polymerase chain reaction with real-time product detection in 21 patients with this disease. We have found the association of chronic hepatitis C with the presence of unfavorable TT genotype of gene IL28B polymorphism rs12979860, which can be regarded as a predictor of the development of this pathology. Favorable genotypes of CC rs12979860 and TT polymorphism of rs8099917 of gene IL28B are more common in healthy individuals and they are associated with higher activity of the inflammatory process in patients with chronic hepatitis C. Therefore, gene IL28B polymorphisms can affect not only the outcome of an acute viral infection but also the further course of chronic hepatitis C.

Role of the IL28B Rs12979860 C/T Polymorphism on the Incidence of Clinically-Active Cytomegalovirus Infection in Autologous Stem Cell Transplant Patients

BackgroundCMV infection represents one of the main cause of morbility and mortality after stem cell transplantation. Type III interferons (IFNs), including IFNl1 (IL29), IFNl2 (IL28A) and IFNll3 (IL28B), are thought to display potent antiviral and immunemodulatory properties in vivo, which may overlap partially with those exerted by type I IFNs. Type I and Type III IFNsl both generate an antiviral state by triggering the JAK-STAT pathway, ultimately upregulating the expression of interferon-stimulated genes.Rs12979860 single nucleotide polymorphism (SNP) in IL28B gene region is well known to influence the spontaneous and treatment-induced clearance in HCV infection. Data on the relevance of such a SNP in other viral infections is still debated even, Bravo et al. recently documented a protective effect of the T allele against CMV infection in the Allogenic stem cell transplantation (Allo-SCT) (Journal of Medical Virology 2014.86:838).Aim of the study: the current study was aimed at investigating whether the IL28B polymorphism rs12979860 may effect on the incidence rate of clinically-relevant active CMV infection in the Autologous stem cell transplantation setting.Patients and methods: From October 2014 45 patients were included in the study because underwent a autologous stem cell transplantation for hematological diseases. The median age of the patients was 56 years (16-66 years). Patients were distributed according to Hematologic disease as following: 73% of the patients had Multiple Myeloma, 20% non Hodgkin Lymphoma, 5% Hodgkin Lymphoma e 2% Acute Myeloid Leukemia.The rs12979860 IL28B SNP (C/T) genotype was determined by Melthing analysis on DNA derived from peripheral blood samples.CMV DNAemia was determined by quantitative Real-Time PCR with a limit detection of 50 copies/mL (Artus, Qiagen). Patients were monitored for CMV DNAemia weekly for the three months after stem cell transplantation.RESULTS: CC genotype was detected in 51% of patients, CT genotype in 35.5% and TT genotype only in 13.5% of patients according to the lowest frequency of TT genotype harboring in general population. A clinically-active CMV infection was documented respectively in 66,6%, 17,4% and 12,5% of patients carrying TT, CT and CC genotype.A trend towards a higher incidence of clinically-active CMV infection was noted in the TT population with respect to CT and CC population (TT vs CC: P= 0.03 and TT vs CT: P=0.02).The duration and peak of CMV-DNAemia levels tended to be higher in patients carrying the TT genotype then in ones with CC or CT genotype, although statistical significance was not reached.A positive correlation was observed between day 7 post ASCT CMV-DNAemia and the monocytes and neutrophils count. By the contrast, a negative correlation was found between day 21 post ASCT CMV-DNAemia levels and the monocytes count on 35th and 45th days after ASCT.ConclusionsIn conclusion, our data suggest that patients with TT genotype have higher incidence of clinically-active CMV infection in Auto-SCT setting. Even though these results should be confirmed by a larger sample size, the lowest prevalence of TT genotype in general population and higher (66.6%) clinically-active CMV infection in TT genotype patients strongly support our data. DisclosuresNo relevant conflicts of interest to declare.

Duplex High-Resolution Melting Assay for the Simultaneous Genotyping of IL28B rs12979860 and PNPLA3 rs738409 Polymorphisms in Chronic Hepatitis C Patients.

Chronic hepatitis C (CHC) is a major burden for public health worldwide. Although newer direct-acting antivirals show good efficacy, their cost precludes their wide adoption in resource-limited regions. Thus, strategies are being developed to help identify patients with high susceptibility to response to classic PEG-interferon + ribavirin therapy. IL28B polymorphism rs12979860 C/T is an important predictor for an efficient response to interferon-based therapy. A genetic variant in adiponutrin (PNPLA3) gene, rs738409 C/G, is associated with steatosis, severity, and progression of liver fibrosis in CHC patients, and predicts treatment outcome in difficult-to-cure HCV-infected patients with advanced fibrosis. We developed a rapid and inexpensive assay based on duplex high-resolution melting (HRM) for the simultaneous genotyping of these two polymorphisms. The assay validation was performed on synthetic DNA templates and 132 clinical samples from CHC patients. When compared with allele-specific PCR and sequencing, our assay showed 100% (95% CI: 0.9724–1) accuracy, with 100% sensitivity and specificity. Our assay was robust against concentration and quality of DNA samples, melting curve normalization intervals, HRM analysis algorithm, and sequence variations near the targeted SNPs (single nucleotide polymorphism). This duplex assay should provide useful information for patient-oriented management and clinical decision-making in CHC.

IL28B gene polymorphisms in mono- and HIV-coinfected chronic hepatitis C patients.

Introduction: Single-nucleotide polymorphisms (SNPs) associated with hepatitis C virus (HCV) clearance were identified near the IL28B gene. Coinfection by the human immunodeficiency virus (HIV) influences the course of HCV contributing to liver damage. Nevertheless, little is known about the relationship between these SNPs and HCV/HIV coinfection. Our aim was to estimate the frequencies of the allelic and genotypic variants of the IL28B polymorphisms rs12979860 (C/T) and rs8099917 (T/G) and their possible association with the establishment of HCV infection.Methodology: A total of 199 non-infected controls and 230 patients with chronic hepatitis C, including 53 coinfected with HIV, participated in the study. Genotyping consisted of polymerase chain reaction and subsequent analysis of the restriction patterns resulting from exposure to endonucleases.Results: Among the controls with established results, 47.4% (90/190) exhibited the rs12979860 CC genotype, 43.7 CT, and 8.9% TT, whereas 29.1% (66/227), 51.5%, and 19.4% of the patients exhibited the CC, CT, and TT genotypes, respectively. With respect to rs8099917, 66.8% (133/199) of the controls exhibited the TT genotype, 31.2% TG, and 2.0% GG, whereas 56.1% (129/230), 40.9%, and 3.0% of the patients exhibited the TT, TG, and GG genotypes, respectively.Conclusion: The frequencies of the rs12979860 C allele and CC genotype and of the rs8099917 T allele and TT genotype were significantly higher among controls compared with patients, thus confirming the suggested protective effect against HCV infection. No significant difference was observed in the genotype and allelic distributions between the mono- and coinfected patients.

Absence of correlation between IL-28B gene polymorphisms and the clinical presentation of chronic hepatitis B in an Amazon Brazilian population.

Objective. The present study investigated the prevalence of the IL-28B polymorphisms rs12979860 and rs8099917 in chronic hepatitis B patients from a case study in Eastern Amazonia. Methods. In total, 65 chronically infected HBV patients and 97 healthy subjects who were anti-HBc and anti-HBs positive (control group) were evaluated between May 2011 and December 2012. The groups of patients were designated as inactive carriers, chronic hepatitis without cirrhosis, and chronic hepatitis with cirrhosis based on clinical, pathological, biochemical, hematological, and virological variables. The patients were genotyped using quantitative real-time PCR. Results. The frequencies of the rs12979860 polymorphism were similar between the infected group (32.3% CC, 41.5% CT, and 26.2 TT) and the control population (35% CC, 47.4% CT, and 17.6% TT), and the frequencies of the rs8099917 polymorphism (7.7% GG, 35.4% GT, and 56.9% TT versus 7.2% GG, 35.1% GT, and 57.7% TT) were also similar in both groups. The associations between the rs12979860 and rs8099917 polymorphisms and the clinical manifestations were not statistically significant. Conclusion. In conclusion, these polymorphisms had a similar distribution between infected and control groups, indicating that they were not associated with susceptibility and the clinical evolution of hepatitis B in the examined population.

Importance of IL-10 and IL-6 during chronic hepatitis c genotype-1 treatment and their relation with IL28B

This paper investigates serum levels of interleukin 10 (IL-10) and interleukin 6 (IL-6) in patients with chronic hepatitis C genotype 1 (CHC-GT1), the relation of each with clinical and virological characteristics, how they affect the response to combined therapy and their relation with the IL28B polymorphisms rs12979860. Serum level expression and the polymorphism of IL-10, IL-6 and IL28B were determined in 138 CHC-GT1 patients, treated with pegylated interferon/ribavirin (pegIFN-α/RBV) for 48weeks, in the following samples: baseline, week-12 (during treatment) and week-72 (post-treatment). 77 patients (56%) presented Sustained Virological Response (SVR) and 61 (44%) were non-SVR. Multivariate logistic regression showed that age⩽40years (aOR=3.7, 95%CI=1.5–8.9, P=0.004), low activity of gamma glutamyl transferase (GGT) (aOR=0.9, 95%CI=0.98–0.99, P=0.028), CC genotype of IL28B polymorphim (aOR=2.7, 95%CI=1.0–7.2, P=0.044) and low IL-6 (aOR=0.5, 95%CI=0.3–1.0, P=0.038) were predictor factors of virological response. In all patients, following treatment, IL-6 decreased at week-12 (P=0.004) from baseline and had returned to basal values at week-72. Serum IL-10 concentration was significantly decreased at week-72 only in SVR patients (P⩽0.001). When patients were stratified by IL28B polymorphisms rs12979860 CC vs non-CC patients, a statistically significant decrease in IL-10 at week-72 in both groups was observed (P=0.003 and P⩽0.001, respectively). None of the polymorphisms of IL-10 or IL-6 studied were associated with SVR. ConclusionsCC genotype of IL28B and low IL-6 serum concentration are factors associated independently with SVR. Moreover, decreased IL-10 at week-72 is associated with SVR in both CC and non-CC patients, and both factors are important to determine the effectiveness of treatment.

PMO-183 Role of IL28B polymorphism in prediction of response to therapy in patients with genotype 1 chronic hepatitis c infection

IntroductionPatients with chronic hepatitis C virus (HCV) infection have a variable response to antiviral therapy with pegylated interferon and ribavirin. Influences include age, gender, viral genotype, viral load, severity of...

1335 IL28B POLYMORPHISM IN HIV-POSITIVE PATIENTS WITH ACUTE HEPATITIS C

(P=0.004). ISGs were significantly higher at baseline in CT/TT haplotypes compared to CC haplotype (P = 0.004). Conclusions: Carriers of the CC haplotype of IL28B polymorphism rs12979860 were more likely to have a robust innate immune response to interferon compared to CT/TT haplotypes, which may contribute to improved viral kinetics, host IFN gene expression, and virologic clearance. High baseline ISG expression and poor host virologic response to IFN based therapy may involve aberrant induction of innate immune response in CT/TT haplotype patients.

Quantitation of pretreatment serum interferon-γ-inducible protein-10 improves the predictive value of an IL28B gene polymorphism for hepatitis C treatment response

Polymorphisms of the IL28B gene are highly associated with sustained virological response (SVR) in patients with chronic hepatitis C treated with peginterferon and ribavirin. Quantitation of interferon-γ-inducible protein-10 (IP-10) may also differentiate antiviral response. We evaluated IP-10 levels in pretreatment serum from 115 nonresponders and 157 sustained responders in the Study of Viral Resistance to Antiviral Therapy of Chronic Hepatitis C cohort, including African American (AA) and Caucasian American (CA) patients. Mean IP-10 was lower in sustained responders compared with nonresponders (437 ± 31 vs 704 ± 44 pg/mL, P < 0.001), both in AA and CA patients. The positive predictive value of low IP-10 levels (<600 pg/mL) for SVR was 69%, whereas the negative predictive value of high IP-10 levels (>600 pg/mL) was 67%. We assessed the combination of pretreatment IP-10 levels with IL28B genotype as predictors of treatment response. The IL28B polymorphism rs12979860 was tested in 210 participants. The CC, CT, and TT genotypes were found in 30%, 49%, and 21% of patients, respectively, with corresponding SVR rates of 87%, 50%, and 39% (P < 0.0001). Serum IP-10 levels within the IL28B genotype groups provided additional information regarding the likelihood of SVR (P < 0.0001). CT carriers with low IP-10 had 64% SVR versus 24% with high IP-10. Similarly, a higher SVR rate was identified for TT and CC carriers with low versus high IP-10 (TT, 48% versus 20%; CC, 89% versus 79%). IL28B genotype and baseline IP-10 levels were additive but independent when predicting SVR in both AA and CA patients. When IL28B genotype is combined with pretreatment serum IP-10 measurement, the predictive value for discrimination between SVR and nonresponse is significantly improved, especially in non-CC genotypes. This relationship warrants further investigation to elucidate the mechanisms of antiviral response and prospective validation.