Interleukin 28B Gene Polymorphisms Research Articles

Interleukin 28B Polymorphism as a Predictor of Sustained Virological Response to Sofosbuvir-Based Therapy for Hepatitis C Virus Patients.

In various genome-wide correlation studies, interleukin (IL)28B gene polymorphism has been strongly correlated with both the therapeutic and spontaneous mediated clearance of hepatitis C virus (HCV). Therefore, this study aimed to evaluate the genotype and allele frequency distributions of IL28B (rs12979860) in patients with chronic hepatitis C and assess the IL28B polymorphisms as predictors of sustained virological response to SOF-based therapy for HCV in Egyptian patients. This retrospective case-control study was conducted on 54 chronic HCV patients who completed treatment with SOF/DCV ± RBV for 12 weeks and responded to treatment with SVR12 (the responder group) as a control group, and 54 chronic HCV patients who completed treatment with SOF/DCV ± RBV for 12 weeks and did not respond to treatment and failed to achieve SVR12 (the non-responder group) as a case group. The CC genotype frequency of IL-28B (rs12979860) was greater in the responder group (51.9%). In contrast, the TT genotype frequency was higher in the non-responder group (48.1%) (p < 0.001), and the T allele significantly increased the risk of non-responses by 3.13 fold. Therefore IL-28B (rs12979860) SNP could be used as a genetic predictor of sustained virological response to SOF+DCV ± RBV-based HCV treatment in Egyptian patients.

Kronik Hepatit B Enfeksiyonu ile İnterlökin-28B Gen Polimorfizminin İlişkisi

Aim: Interleukin 28B (IL28B) gene polymorphism may play a role in hepatitis B virus (HBV) infection prognosis. We investigated the effects of IL28B gene polymorphism on viral clearance and viral load in chronic hepatitis B (CHB) patients.Material and Methods: We included 146 individuals who applied to our center between October 2011 and October 2012. CHB (N=117) and control (N=29) groups were compared in terms of IL28B gene rs12979860, rs12980275 gene region polymorphisms, and IL28B gene expression (mRNA) levels.Results: There was no statistically significant difference between groups in terms of rs12979860 gene region polymorphism rates (χ2=0.36, p=0.835). But there was a significant association between groups in terms of rs12980275. In the CHB group, the A/A genotype was much more, (χ2=55.2, p&amp;lt;0.001), G/A and G/G genotypes were less frequent. There was no statistically significant difference between the groups in terms of IL28B expression levels.Conclusion: This study revealed the genotype profile of the IL28B gene of our region. It is the first study on this subject in our region. The association between CHB and rs12980275 polymorphism may be important. Our results will contribute to future studies.

Impact of IL-28B gene polymorphism on chronic hepatitis-C patients progression with diabetes and non-diabetes

BackgroundChronic hepatitis C (CHC) is a silent viral infection; however, elevated mortality and morbidity rates are noted in Egypt due to its adverse effects. The augmented incidence of diabetes in patients with viral C infection may be owing to glucose intolerance, high BMI, senility, and inherited factors.Purpose of the studyLittle information is available about the connection between interleukin-28B (IL-28B) genotype in disease progression among CHC patients with diabetes. Thus, we aimed to assess the association between IL-28B genotype (rs12979860) in CHC with type 2 diabetes mellitus (T2DM) versus those without diabetes in disease progression among Egyptian patients.ResultsCC genotype was significantly lower in diabetics than in non-diabetics (13.7% vs. 36.3%). While (CT/TT) were significantly higher in diabetics than in non-diabetics (CT 58.8% vs. 43.7%), (TT 27.5% vs. 20%) (p = 0.03) and likewise alleles (p = 0.04). Multivariate logistic regression analysis was significant with viral load p < 0.001, alanine aminotransferase (ALT) p < 0.001, genotype CC versus TT p = 0.04 & T2DM p = 0.03.ConclusionCC genotype might be used as a protective factor and TT genotype as a risk factor in disease progression among CHC patients with T2DM. Additionally, viral load, ALT & T2DM might interplay as predictors of disease severity. Detecting the genetic factors can be helpful in predicting and preventing the complications of diabetes associated with the hepatitis C virus (HCV).

The relation between interleukin 28B gene polymorphisms (rs8099917 and rs12980275) and the response of treatment of Hepatitis C Virus genotype 4 patients to Sofosbuvir and Daclatasvir therapy

Background: The main line of treatment of hepatitis C in Egypt is direct acting antiviral drugs (DAAs) Objectives: the current study aimed to explore the effect of IL28B genetic polymorphism on HCV infection progression and response to the new treatment in difficulty to treat individuals with HCV genotype 4. Methods: we collected blood samples from 50 healthy individuals as a control and 150 HCV- patients receiving SOF/DCV with ribavirin combination. IL28B (rs8099917, rs12980275) genotyping was implemented using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method to detect its impact on HCV disease outcome. Results: Out of patients, 141(94%) were responders to treatment and 9 (6%) were non- responders. A total of 112 (74.7%) of patients belonged to mild to moderate stages of liver fibrosis and 38(25.3%) had moderate to severe stages. There was a significant increase in severity of fibrosis among non-responders (p value .0.05). significant differences between the different genotypes of IL28B rs12980275 are not detected among the study population. Conclusion: TT genotype of IL28B (rs8099917) may be a protective factor against infection and associated with probability of achieving SVR to combined SOF and DCV therapy in genotype 4 HCV patients. However, GG genotype is negatively associated with HCV infection outcome. IL28B rs12980275 variants had no association with HCV infection.

Interferon-γ inducible protein-10 and interleukin 28B gene polymorphism as predictive markers for genotype 4 hepatitis C virus treatment response.

HCV genotype 4 dominates the HCV epidemic in Egypt. Drug resistance was the most serious side effect that reflects bad clinical outcome. Several studies had demonstrated that baseline serum interferon-γ-inducible-protein 10 (IP-10) levels and interleukin 28B polymorphisms were associated with the resistance to the standard of care pegylated interferon alpha and ribavirin (PEG-IFNα/RBV) therapy and development of post-treatment relapse. Our purpose was to assess the predictive value of combining IP-10 levels and IL28B genotypes to PEG-IFNα/RBV therapy response in Egyptian chronic HCV infection patients with genotype 4. Ninety Egyptian patients chronically infected by HCV genotype-4 treated with pegylated interferon alpha and ribavirin (PEG-IFNα/RBV) therapy were enrolled. Serum IP-10 levels were determined by enzyme linked immunosorbent assay pre- and post- treatment. IL-28B (rs12979860 and rs8099917) polymorphisms were performed by PCR-RFLP in all patients. Overall, 38 patients (42.2%) achieved sustained virologic response (SVR) and 52 (57.8%) patients have non-viral response (NVR). Pretreatment serum IP-10 mean levels were significantly lower in patients who achieved SVR than in NVR (P<0.05). CC genotype in IL28B polymorphism (rs12979860) was the favorable genotype as 65.8% achieved SVR, while TT genotype in IL-28B polymorphism (rs8099917) was the favorable genotype as 81.5% achieved SVR. Baseline IP-10 was significantly correlated to genotypes CC in rs12979860 and TT in rs8099917. Combined use of serum baseline IP-10 levels with IL-28B polymorphisms could improve the prediction of SVR to PEG-IFNα/RBV therapy in Egyptian chronic HCV infection patients with genotype 4.

The Study of IFNL3 Gene Rs12979860 Polymorphism in the Hepatitis C Virus Patients and Healthy Population in Tehran Province, Iran

Background: Hepatitis C virus (HCV) infection can lead to a number of disorders and subsequent failures, including chronic liver disease and cancer. Genotype rs12979860 CC is an interleukin 28B gene polymorphism associated with an adequate response to treatment in HCV patients. However, its response quality varies in different races and populations. Objectives: The present study aimed to investigate this polymorphism in the Iranian population. Methods: In this study, 120 volunteers were evaluated as patient subjects and 120 volunteers as the control subject group. The collected serum samples were examined by the PCR-RFLP technique and the frequency of polymorphism at rs12979860 was tested in both groups. Results: The findings of this study showed that the risk of HCV infection in the subjects with CC genotype of IL-28B gene was less than (OR = 2.000, P = 0.009) that of subjects with other genotypes of rs12979860 polymorphism, including CT and TT. The frequency of genotypic variations of rs12979860 gene in patients were as CC = 33.3%, CT = 43.3%, TT = 23.3%, and in healthy subjects accorded with CC = 50%, CT = 32%, TT = 17%. A significant difference was also observed between the two healthy and HCV suffering groups in terms of gender (P < 0.02). Conclusions: In HCV patients, the frequency of CC variation in IL-28B rs12979860 gene leads to a more effective response to treatment than other genotypes in HCV patients. Also, the frequency of CC in healthy people was higher than patients.

IL-28B genetic variation, gender, age, jaundice, hepatitis C virus genotype, and hepatitis B virus and HIV co-infection in spontaneous clearance of hepatitis C virus.

Spontaneous viral clearance observed in some patients is one of the variants of the hepatitis C virus (HCV) infection natural history. We aimed to look at the complexity of factors affecting the spontaneous clearance of HCV (SC HCV). A total of 357 anti-HCV positive patients (309 with chronic hepatitis C and 48 patients with SC HCV) were included into the study. We studied the effects of the interleukin-28B (IL-28B) gene polymorphism, gender, age, the routes of virus transmission, past hepatitis C with jaundice, HCV genotype, and hepatitis B virus (HBV) and HIV co-infection on the outcome of HCV infection. Based on the study results, the SC HCV was found in 48 individuals (13.4%). The most significant positive factors affecting the SC HCV included IL-28B single nucleotide polymorphism (SNP) rs12979860 (CC) and SNP rs8099917 (TT) (OR 4.03, p<0.001) and (OR 3.14, p<0.002), female gender (OR 2.72, p<0.001), young age (OR 2.30, p<0.008), and past history of jaundice (OR 5.12, p<0.001). The markers of a past HBV infection were found significantly more often in SC. Positive predictors of the SC HCV include favorable IL-28B genotype, female gender, young age, a history of jaundice, markers of a past HBV infection, the absence of HIV infection, but not the viral genotype.

The interleukin 28B gene polymorphism, rs8099917, in patients with chronic hepatitis C and response to the treatment with pegylated interferon and ribavirin.

Background:The present study aimed to determine the frequency of the IL28B polymorphism rs8099917 in patients with genotype 1 hepatitis C virus (HCV) infection treated with pegylated-interferon-α2b (PEG-IFN-α2b) and ribavirin (RBV) and its treatment outcome.Materials and Methods:The IL28B rs8099917 genotypes were determined among 100 HCV-infected patients and the viral load was also estimated. PEG-IFN-α2b and RBV combination were administrated to the patients for 48 weeks and the treatment outcome was defined.Results:Sixty-seven (67%), 27 (27%), and 6 (6%) of 100 patients were determined as TT, GT, and GG genotype, respectively. The response rate to treatment was significantly higher in patients with TT genotype.Conclusion:According to the results of the present study, patients with IL28B rs8099917 TT genotype achieve higher sustained virological response than the GT and GG genotypes. Thus, when there are no alternatives, treatment with PEG-IFN-α2b and RBV combination can be suggested in patients with IL28B TT genotype.

Comparison of IL-28B favorable genotype frequency between healthy and patients infected with HCV

Introduction: Combination of interferon-alpha (IFN-α) and Ribavirin (RBV) drugs is used for treatment of hepatitis C virus (HCV) chronic infection. Various factors play role in the response rate of HCV infected patients to treatment. HCV genotype along with viral load, age, race, obesity, insulin resistance, fibrosis and interleukin 28B gene (IL-28B) polymorphisms are considered the most important ones. In recent years, it has been claimed that some polymorphisms close to IL-28B gene play a significant role in response to combined therapy among which IL-28B polymorphisms have a more important role in sustained virological response (SVR). In this study, frequency of genotypes of rs8099917 polymorphism of interleukin 28B gene in 2 groups of Iranian healthy individuals and HCV infected patients living in Tehran was compared. Materials & Methods: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to compare the frequency of genotypes of rs8099917 polymorphism between 105 healthy individuals and 105 chronic HCV infected patients. The results were analyzed with SPSS version 15 using χ2 test. Findings: The genotype frequency of this polymorphism in the healthy individuals was demonstrated as GG: 1%, GT: 25.7% and TT: 73.3%, while in HCV infected patients, it was shown as GT: 58.1% and TT: 41.9%.. No GG genotype was detected in the patients infected with HCV. Discussion & Conclusion: Our investigation came to the conclusion that a significant difference existed between the 2 groups of Iranian healthy and HCV infected individuals regarding the frequency of rs8099917 genotypes and frequency of favorable TT genotype, because it was higher among the healthy individuals than that of the patients infected with HCV

IL28B gene polymorphism rs12979860, but not rs8099917, contributes to the occurrence of chronic HCV infection in Uruguayan patients

BackgroundHost single-nucleotide polymorphisms (SNPs) near the interleukin 28B (IL28B) locus are associated with sustained virological response to antiviral therapy and with spontaneous Hepatitis C Virus (HCV) clearance. Prevalence of these SNPs varies depending on ethnicity. The impact of IL28B SNPs in HCV-infected patients is currently unknown in Uruguay. Therefore, the aim of this study was to evaluate and compare the distribution of polymorphisms in the IL28B gene (rs12979860 and rs8099917) among HCV-infected patients and healthy individuals in Uruguay and thus assess their possible association with the establishment of HCV infection.MethodsDNA was recovered from 92 non-infected individuals and 78 HCV-infected patients and SNPs were determined by RFLP and allelic discrimination by real-time PCR.ResultsThe distribution of rs12979860 genotypes for the infected population was 29.5%-CC, 47.4%-CT and 23.1%-TT and for the control group 45.7%, 42.4% and 11.9%, respectively. Prevalence in both infected and uninfected individuals is similar to that reported in other countries with admixed populations. The distribution of rs8099917 genotypes for the infected population was 57.7%-TT, 27.2%-TG and 14.1%-GG and for the control group 60.9%, 33.7% and 5.4%, respectively. The comparison of rs12979860 genotype distribution between the two populations evidenced a higher prevalence of the favourable genotype (CC) in the uninfected control group (p < 0.05). Additionally, results generated using logistic regression analysis show that individuals carrying rs12979860-TT or CT genotypes have a higher likelihood of developing chronic hepatitis upon infection with HCV, when compared to CC carriers, considering rs8099917 genotype as constant.ConclusionPatients with HCV infection have a statistically significant lower prevalence of the favourable rs12979860 genotype when compared to uninfected individuals; therefore we can establish that only IL28B rs12979860-CT and TT genotypes seem to contribute to the occurrence of chronic HCV infection in the cohort of Uruguayan population studied. Considering that a trend towards a higher frequency of “good” response genotypes was observed in responder patients, we believe that IL28B rs12979860 genotyping could be a useful tool for predicting different therapies outcome, including in the DAA era.

Distribution of IL28B and IL10 polymorphisms as genetic predictors of treatment response in Pakistani HCV genotype 3 patients.

There are over 10 million hepatitis C virus (HCV)-infected patients in Pakistan. For these patients, a combination of interferon with ribavirin is the most economical and easily available treatment. Single-nucleotide polymorphisms in interleukin genes have been reported to be associated with the pathogenesis and clearance of HCV, and sustained virologic response (SVR). An interleukin 28B (IL28B) gene polymorphism has been shown to modify treatment outcomes, but the effects of interleukin 10 (IL10) polymorphisms have not been previously assessed in the Pakistani population. The present study was conducted with 302 subjects categorized into two groups: 100 healthy volunteers (Group I) and 202 patients with chronic HCV (Group II). Patients within Group II were further divided into two subgroups according to therapeutic response: SVR (responders = 132) and NR (non-responders/relapsers = 70). IL28B (rs8099917, rs12979860) and IL10 (rs1800872, rs1800871, rs1800896) gene polymorphisms were studied in all subjects. A significant difference in the distribution of IL28B rs12979860C/T genotypes between the two groups (p<0.05) was observed, while of the three IL10 polymorphisms, a significant difference was only shown for rs1800896 A/G. Haplotype analysis (IL28B and IL10) showed a significant association of TTGTC and TTGTA when comparing the groups. There was a strong association of the favorable alleles rs8099917T and rs12979860C in the SVR group as compared with the NR group (p<0.05), and rs1800896 also showed an association with the SVR group as compared to the NR group (p<0.004). Haplotype analysis showed significant associations when comparing the SVR and NR subgroups, i.e. TCATC (p=0.009), TTGTA (p=0.005), TCATA (p<0.0005), TCACA (p=0.002), GTGCC (p=0.002) and TCGTC (p=0.005). IL28B (rs8099917 and rs12979860) and IL10 (rs1800896) polymorphisms alone, or in combination, are good predictors of therapeutic response in HCV-3a patients.

Association of interleukin-28B polymorphisms with platelet count and liver function recovery after liver transplant.

The present genome-wide association study investigated the relationship of interleukin 28B (IL-28B) genetic variants with HBV susceptibility and prognosis of HBV-infected patients. This study aims to examine the role of IL-28B polymorphisms on transplant etiologies and the liver function recovery in Chinese liver transplant recipients.A total of 231 liver transplant recipients were enrolled in the study. The transplant etiologies included progressive HBV hepatitis, HBV-related liver cirrhosis (LC), HBV-related hepatocellular carcinoma (HCC), and non-HBV-related disease. All recipients were in stable condition before transplantation. Three single nucleotide polymorphisms (SNPs) of IL-28B (rs12979860, rs12980275, rs8099917) of recipients were analyzed by high-resolution melting (HRM) curve analysis. Liver function, blood cell count, and coagulation function were regularly tested before and for next 5 years after transplantation.No significant association was found between IL-28B gene polymorphisms and transplant etiologies. Peripheral platelet count in the third and fourth days after transplantation were significantly higher in recipients carrying IL-28B rs12979860 T allele, or rs8099917 C allele (P < .016666667), while there were no significant differences between these variants and International Normalized Ratio (INR) levels. In addition, gamma-glutamyltransferase (GGT) levels in recipients with rs12980275 G allele were higher than those in the wide-type recipients before transplantation (P < .016666667, respectively); nevertheless, no influence of these variants on GGT recovery was observed after transplantation.Genetic variations of IL-28B might impact on liver function recovery by influencing peripheral platelet counts and reducing liver inflammation, but have weak association with transplant etiologies.

The association between interleukin-28B gene polymorphisms as a potential biomarker and the risk of chronic Periodontitis in an Iranian population

BackgroundChronic Periodontitis (CP) is a common inflammatory disease affects supporting tissues of the teeth and can lead to tooth loss. The objective of this study was to determine the relationship between polymorphisms in the IL-28B gene and chronic periodontitis in an Iranian population.MethodsTwo hundred and ten CP patients and one hundred healthy subjects were enrolled in the present case-control study. The rs12979860 and rs8099917 SNPs were identified using RFLP and T-ARMS-PCR methods respectively.ResultsSNP analysis revealed that the G allele of rs8099917 SNP and T allele of rs12979860 SNP increased susceptibility to CP compared to the A allele and C allele (p < 0.0001, OR = 2.712, CI = 1.783-4.126; p < 0.0001, OR = 2.538, CI = 1.784-3.613 respectively). In addition, the CT/GT, TT/GG and TT/GT haplotypes were predominant in CP patients and significantly associated with the increased risk of CP.ConclusionIL-28B polymorphisms may be useful predictive factors for chronic periodontitis and correlated to the susceptibility to CP infection in our population.

Spontaneous Viral Load Decline and Subsequent Clearance of Chronic Hepatitis C Virus in Postpartum Women Correlates With Favorable Interleukin-28B Gene Allele

Postpartum hepatitis C viral (HCV) load decline followed by spontaneous clearance has been previously described. Herein we identify predictors for viral decline in a cohort of HCV-infected postpartum women. Pregnant women at Cairo University were screened for anti-HCV antibodies and HCV RNA, and viremic women were tested for quantitative HCV RNA at 3, 6, 9, and 12 months postpartum. Spontaneous clearance was defined as undetectable viremia twice at least 6-months apart. Associations between viral load and demographic, obstetrical, HCV risk factors, and interleukin-28B gene (IL28B) polymorphism (rs12979860) were assessed. Of 2514 women, 97 (3.9%) had anti-HCV antibodies, 54 (2.1%) were viremic and of those, 52 (2.1%) agreed to IL28B testing. From pregnancy until 12 months postpartum, IL28B-CC allele women had a significant viral decline (P = .009). After adjusting, the IL28B-CC allele had a near significant difference compared to the CT allele (odds ratio [OR], 0.75; 95% confidence interval [CI], 0.75,1.00; P = .05), but not the TT allele (OR, 0.91; 95% CI, 0.61,1.38; P = .64). All 14/52 (26.9%) women who subsequently cleared were among the 15 with undetectable viremia at 12 months, making that time point a strong predictor of subsequent clearance (sensitivity = 100%, specificity = 97.4%, positive predictive value = 93.3%, negative predictive value = 100%). IL28B-CC genotype and 12-month postpartum undetectable viremia were the best predictors for viral decline and subsequent clearance. These 2 predictors should influence clinical decision making.

Interferon λ3 gene (IL28B) is associated with spontaneous or treatment-induced viral clearance in hepatitisC virus-infected multitransfused patients with thalassemia.

Hepatitis C virus (HCV) is the major posttransfusion infection in multitransfused individuals in India with thalassemia major. To our knowledge, this study is the first conducted to correlate and comprehend the effects of the host interleukin (IL)28B gene polymorphism at loci rs12979860 and rs8099917 in spontaneous or interferon (IFN)-induced treatment response in the HCV-seroreactive individuals with thalassemia major. A total of 557 HCV-seroreactive individuals with thalassemia were processed for HCV viral genotyping and host IL28B single-nucleotide polymorphism analysis at loci rs12979860 and rs8099917. Of 557 individuals, 70.92% were found to be HCV RNA positive with Genotype 3 (95.18%) as predominant strain. A favorable CC allele at locus rs2979860 and TT allele at rs8099917 were 75.31 and 77.16%, respectively, which was strongly associated with spontaneous clearance of infection (p < 0.05). Of 85 IFN-treated cases, 56 achieved sustained virologic response (SVR) whereas 27 were relapsed cases. Among these patients who achieved SVR, a favorable CC/TT allele at rs12979860/rs8099917 was found to be predominant with 76.79 and 66.07%, respectively, whereas in the case of relapsed patients, unfavorable CT (55.56%) and TG (59.26%) alleles were found to be predominant. Additionally, low serum ferritin level was significantly associated with SVR. CC at rs12979860 and TT at rs8099917 was strongly associated with spontaneous clearance and SVR in the population with thalassemia. Low age group and low serum ferritin level are important cofactors. This allelic pattern will aid clinicians in making an informed decision about prognosis and therapeutic management.

The effects of interleukin-28B gene polymorphisms on antiviral treatment response in patients with chronic hepatitis C

Objective To investigate the relationship between interleukin (IL)-28B gene polymorphisms (rs12979860 and rs8099917) and treatment response in patients with chronic hepatitis C in China. Methods Taqman probes single nucleotide polymorphism genotyping methods were used to detect the genotypes of rs12979860 (C/T) and rs8099917 (T/G) located at IL-28B gene in 105 included patients. The patients were treated with standard doses of pegylated interferon plus ribavirin and were followed up regularly for therapeutic response and adverse reaction. The relationship between IL-28B gene polymorphism and antiviral treatment response of patients were analyzed. Categorical data were analyzed using Pearson chi-square test or Fisher exact test. Results Totally 105 cases were included in our study and 2 cases lost to follow-up because of moving away. Eight-one cases (78.6%) of the remaining 103 patients were CC/TT genotype (CC/TT group) at rs12979860 and rs8099917, 19 cases (18.4%) were CT/TG (CT/TG group) and 3 cases (2.9%)were TT/TG (TT/TG group). No other genotypes were detected and linkage disequilibrium was discovered at the two polymorphism loci (r2=0.11). After 4 weeks of treatment, 35 cases (43.2%) in CC/TT group, 3 cases (15.8%) in CT/TG group and non in TT/TG group achieved rapid virological response (RVR). There were statistically significant differences among three groups (P=0.033). After 12 weeks of treatment, 45 cases (55.6%) in CC/TT group, 6 cases (31.6%) in CT/TG group and none in TT/TG group achieved early virological response (EVR). There were statistically significant differences among three groups (P=0.025). At the end of the treatment, 68 cases (83.9%) in CC/TT group, 10 cases (52.6%) in CT/TG group and only 1 case (33.3%) in TT/TG group achieved end-of-treatment response (ETR). There were significant statistical differences among the three groups (P=0.003). After 24 weeks of follow-up, 62 cases (76.5%) in CC/TT group, 9 cases (47.4%) in CT/TG group and 1 case (33.3%) in TT/TG group achieved sustained virological response (SVR). There were statistically significant differences among the three groups (P=0.014). One hundred and one cases in CC/TT group developed adverse events, among them 19 cases needed clinical treatment. There were 43 cases in CT/TG group developed adverse events and 9 cases needed treatment. Seven cases in TT/TG group developed adverse events and only 1 case needed treatment. There were no statistically significant difference among three groups (χ2=0.139, P>0.05). Conclusions The genotype of rs12979860 (C/T) and rs8099917 (T/G) at IL-28B gene could affect the treatment response in patients with chronic hepatitis C. RVR and SVR are higher in patients with genotype CC/TT, which might help to guide HCV treatment. Key words: Interleukin-28B; Hepatitis C, chronic; Polymorphism, single nucleotide; Antiviral response

Lack of association between interleukin 28B gene polymorphisms (rs8099917G/T, rs12979860 C/T) and susceptibility to chronic hepatitis C virus infection, Tehran, Iran.

Chronic Hepatitis C infection is a critical health problem worldwide, which caused by hepatitis C virus (HCV). Interleukin 28B (IL28B) is a determinant factor in disease progression and also susceptibility to chronic HCV infection. The most significant aim of this study is to analyze the association between IL28B gene polymorphisms with susceptibility to chronic HCV infection in Iranian population. This study follows a case- control study design, in which, 288 patients with chronic hepatitis C and 250 healthy individuals were genotyped for IL28B polymorphisms (rs12979860 C/T and rs8099917 G/T). Studied population collected from Taleghani Haospital, Tehran. Genotyping of IL28B gene polymorphisms were performed using PCR-Restriction Fragment Length Polymorphism (PCR-RFLP) method. 10 percent of the studied population was sequenced to validate the results. rs8099917 G/T and rs12979860 C/T were differently distributed in hepatitis C patients and healthy controls in the female gender. TT, TG and GG genotypes distribution in the female gender were 56.7%, 39.8% and 4.5% in cases and 67%, 31.6% and 1.4% in controls (p=0.54). Also CC, CT and TT genotypes distribution were 31.8%, 61.4% and 6.8% in cases and 51.7%, 44.9% and 3.4% in controls (p=0.2). However, there was no significant difference in the allelic frequency and genotype distribution of rs12979860 C/T and rs8099917 T/G in both HCV patients with genotype 1a and 3a. It seems that rs8099917 G/T polymorphism plays a significant role in susceptibility to chronic HCV infection in Iranian population. On the other hand, no association was found between rs12979860 C/T polymorphisms and chronic hepatitis C.

Prognostic value of the combination of blood group specificity and interleukin 28B gene polymorphism for estimation of efficiency of therapy with the use of pegylated interferon a-2 and ribavarin in patients with chronic genotype 1 hepatitis C

To estimate the prognostic value of the combination of blood group specificity and interleukin 28B gene polymorphism for the achievement of sustained virologic response (SVR) to antiviral therapy (AVT) with the use of pegylated interferon α-2 and ribavarin in patients with chronic genotype 1 hepatitis C (CHC-1). The secondary aim was to evaluate the influence of these genetic factors on the progress of hepatic fibrosis in case of failure of the above treatment. A total of 146 patients with CHC-1 were examined. We studied the RNA genotype of hepatitis C virus, blood group specificity, IL-28B gene polymorphism, and severity of hepatic fibrosis (puncture biopsies). Dynamics of hepatic fibrosis was followed up in 40 patients who failed to develop the virologic response. 20 control patients did not receive AVT. The multifactor significance criterion was used to identify the initial factor that produced the highest effect on SVR. SVR was observed in 56.8% of the patients. Its efficiency was most significantly influenced by. the combination of blood group specificity and interleukin 28B gene polymorphism (p = 0.000024). Combination of blood group (0)1 with C/C or T/T IL-28B genotypes, A(II) with C/T or T/T and B(III) with T/G was associated with SVR in 100, 88.2, and 94.4% cases respectively. It was absent in patients with blood group A(II) in combination with double-nucleotide substitution in rs8099917 of the IL-28B gene (TG and GG genotypes); these patients suffered progressive fibrosis. SVR occurred in 83.8% of the patients with blood group B(III). The knowledge of blood group in patients with CHC-1 and IL-28B gene polymorphism treated with the use of pegylated interferon α-2 and ribavarin allows to predict SVR with a probability of 100% in case of blood group 0(1) and C/C or T/T genotypes, 88.2% in case of blood group A(II) and single-nucleotide C>Tsubstitution in rs8099917 locus of the IL-28B gene, 94.4% in case of blood group B(II) and single-nucleotide T>G substitution in the rs809991.7 locus, 83.8% in case of blood group B(III). Treatment of patients with these genetic traits with antiviral drugs of direct action has no appreciable advances over treatment with AVT in combination with pegylated interferon α-2 and ribavarin (SVR above or around 85%). Patients with blood group A(II) and single- or double-nucleotide substitution in rs8099917 (TG or GG genotypes) have minimal chances to produce SVR to the above treatment. Simultaneous progression of hepatic fibrosis suggest that such therapy is undesirable in these cases. They should be regarded as main candidates for interferon-free therapy. Combination of blood group specificity and interleukin 28B gene polymorphism is a simple and reliable predictor of SVR and dynamics of fibrosis in patients with CHC-I receiving AVT with pegylated interferon α-2 and ribavirin; also, it may be an instrument of selection of patients for interferon-free therapy.

Association of IL28B and IL10 gene polymorphism with predisposition to tick-borne encephalitis in a Russian population

Genetic predisposition to tick-borne encephalitis (TBE) is rather poorly studied in human populations. Human genes encoding crucial components of antiviral immune response are most likely involved in protective mechanisms against TBE virus. Previously, several single nucleotide polymorphisms (SNPs) located in interleukin 28B (IL28B) and interleukin 10 (IL10) genes were associated with predisposition to chronic hepatitis C (caused by a structurally similar virus from the same Flaviviridae family) in a number of human populations. The aim of the present study was to estimate a possible association of the IL28B gene rs8103142 and rs12980275 SNPs and IL10 gene rs1800872, rs3021094, and rs3024498 SNPs with predisposition to TBE in a Russian population. Genotypic and allelic frequencies for these SNPs were analyzed in 132 non-immunized TBE patients (34 with fever, 60 with meningitis, and 38 with severe central nervous system disease) and compared with the population control (221 Novosibirsk citizens). The results obtained suggest that both studied IL28B gene SNPs, as well as the IL10 gene rs1800872 SNP are associated with predisposition to TBE in Russian population.

Association of the Treatment Induced Clearance of Hepatitis C Virus Infection with the IL28B Gene Polymorphisms

Background: It has been shown that single nucleotide polymorphisms (SNPs) near the interleukin 28B (IL28B) gene were associated with sustained viral response following standard treatment of hepatitis C virus infection. Aim: The aim of the study was to evaluate the association between the SNPs near the IL28B gene and the response to the treatment of chronic hepatitis C.