Interleukin 28B Rs12979860 Polymorphism Research Articles

IL28B rs12979860 polymorphism and zinc supplementation affect treatment outcome and liver fibrosis after direct-acting antiviral hepatitis C therapy

BackgroundImpact of interleukin 28B (IL28B) rs12979860 polymorphism on response to direct-acting antivirals agents in HCV genotype 4-infected patients is under investigation. Zinc may have an advantage in improvement of liver damage and treatment outcome. We aimed to evaluate IL28B polymorphism and zinc administration impact on patient response to treatment and amelioration of liver fibrosis. ResultsThree hundred patients on anti-HCV treatments were equally categorized into patients treated with dual therapy (sofosbuvir/ribavirin) for 24 weeks, triple therapy (sofosbuvir/ribavirin+pegylated interferon-alpha) for 12 weeks, dual therapy plus oral zinc and with triple therapy plus oral zinc. All patients were genotyped for IL28B. Sustained virologic response (SVR) was achieved in 100% of patients with CC genotypes while 15.5% of CT/TT carriers did not attain SVR. After treatment, patients with CC genotype showed improvement in liver-related parameters compared with CT/TT genotypes. Zinc supplementation was associated with improved SVR in CT/TT genotypes and liver parameters in both CC and CT/TT genotypes. Hepatic fibrosis was improved in higher percent of CC genotype (16.7%) compared with CT/TT genotypes (5.8%). Interestingly with zinc administration, improved fibrosis increased to 60.9% in CC genotype vs. 15.4% in CT/TT genotypes. ConclusionAbsolute SVR rates in patients with IL28B CC genotype support their selection for shorter treatment duration and therefore associated with high economic value. IL28B polymorphism is associated with improvement of hepatic functions and fibrosis after antiviral treatments. Zinc is powerful supplement not only to increase SVR in non-responders but also to improve hepatic functions and fibrosis.

Programmed cell death-1 rs11568821 and interleukin-28B rs12979860 polymorphisms in autoimmune hepatitis

BackgroundAutoimmune hepatitis (AIH) is a relatively rare chronic liver disease of unknown etiology. The genetic background affects susceptibility, clinical phenotype, and prognosis. The programmed cell death-1 rs11568821 polymorphism (PD1.3) has been associated with susceptibility to autoimmune diseases. The interleukin-28B (IL28B) rs12979860 polymorphism has been associated with steatosis, inflammation, and fibrosis in liver diseases. AimOur aim was to investigate for the first time the incidence and clinical significance of PD1.3 and IL28B rs12979860 in AIH. MethodsTwo hundred patients with AIH were evaluated, while 100 healthy subjects were used as controls. Genotyping was performed with in-house allelic discrimination End-Point PCR. ResultsThe SNP PD1.3/A was present in 36/200 (18%) AIH patients compared to 28/100 (28%) healthy controls (p = 0.065). The AA/GA genotypes were not associated with the mode of presentation of AIH, the histological grade or stage, the presence of cirrhosis, risk of disease progression, response to treatment and survival. The IL28B rs12979860 genotype distribution was CC 79/200 (39.5%), TT 36/200 (18%) and CT 85/200 (42.5%), in similar rates with healthy controls (p = 0.878). Inflammatory activity and fibrosis stage did not differ between CC homozygotes and CT/TT carriers. LDL cholesterol was significantly higher in CC than CT/TT patients (P = 0.027), though no differences was found regarding the presence of steatosis or steatohepatitis. On-treatment response to immunosuppressive treatment was not affected by the IL28B rs12979860 polymorphism. However, CC homozygotes AIH patients achieved treatment withdrawal in significantly higher rates (OR 2.3, 95%CI: 1.1–4.7, P = 0.02) irrespective of the presence of steatosis or steatohepatitis. ConclusionsThe PD1.3 and IL28B rs12979860 variants are unlikely to contribute to AIH susceptibility, disease presentation and prognosis. The IL28B rs12979860 is not associated with the presence of concurrent steatosis or steatohepatitis. However, although on-treatment response rates to immunosuppression were not affected by the IL28B rs12979860 polymorphism, AIH patients with CC homozygosity were more likely to achieve complete treatment withdrawal. This novel finding needs validation and further clarification from larger multicenter studies.

The clinical significance of programmed cell death-1 rs11568821 and interleukin-28b rs12979860 polymorphisms in autommune hepatitis

The clinical significance of programmed cell death-1 rs11568821 and interleukin-28b rs12979860 polymorphisms in autommune hepatitis

THU-204-Analysis of interleukin 28B rs12979860 polymorphism relationship with spontaneous clearance of hepatitis D virus infection in Mongolian population

THU-204-Analysis of interleukin 28B rs12979860 polymorphism relationship with spontaneous clearance of hepatitis D virus infection in Mongolian population

Interleukin 28B rs12979860 genotype and Human Immunodeficiency Virus type 1: Susceptibility, AIDS development and therapeutic outcome

Human Immunodeficiency Virus type 1 (HIV-1) infection and progression varies widely among individuals. Interferon-λ3 exerts anti-HIV function by activating JAK/STAT pathway-mediated innate immunity. Therefore, we aimed to investigate the association between single nucleotide polymorphisms of the interleukin 28B (IL28B) gene, and the risk of acquisition, AIDS development and therapeutic outcome of HIV-1 in a Moroccan population.A total of 266 HIV-1 seropositive and 158 HIV-1 seronegative subjects were enrolled. Genotyping of rs12979860 of the IL28B was performed using a predesigned TaqMan SNP genotyping assay. No significant association was found between IL28B rs12979860 polymorphism and susceptibility to HIV-1 infection and AIDS development (p > .05). However, in HIV-1 treated patients carrying CC genotype had a more pronounced high levels of CD4+ T-cell compared to subjects with TT genotype (p = .0004).Interestingly, regarding HIV-1 viral load no significant differences between IL28B genotypes in treated and untreated patients were observed (p < .05).IL28B rs12979860 polymorphism not influences the susceptibility to HIV-1 and the AIDS development. However, this polymorphism may affect the response to treatment as measured by CD4+ T cell counts.

A comparative study of various methods for detection of IL28B rs12979860 in chronic hepatitis C

Interleukin-28B (IL28B) single-nucleotide polymorphisms (SNPs) constitute important host-related factors influencing the response rate to Hepatitis C virus (HCV) standard antiviral therapy. In the last few years, several new technologies for SNP detection have been developed. However, the sensitivity and specificity of various methods are different and needs evaluation. Five different methods (resolution melting curve [RMC], polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP], PCR-sequencing analysis, amplification refractory mutation system [ARMS], and zip nucleic acid probe-based real-time PCR [ZNA]) were developed for genotyping rs12979860 associated with IL28B. In this study, limit of detection (LD), costs and turnaround time of these methods were compared in 350 subjects. As for IL28B rs12979860 polymorphisms, 348/350 (99.4%) samples were consistent among the five methods, while results for 2/350 (0.57%) samples were concordant by ZNAs and PCR-sequencing, and discordant by other methods. Without considering the cost of DNA extraction, the price of each reaction for ARMS-PCR, RMC, PCR-RFLP, ZNA and PCR-sequencing were respectively: US$3.10, US$5.0, US$5.50, US$8.50 and US$17.0. RMC was the fastest method, while the ZNA method was easy to use, reliable and effective. Lower LD was determined to be 50–60 copies/μL for the PCR-RFLP, RMC and ARMS-PCR assays; whilst ZNA assay was able to detect 2–3 copies/μL. In conclusion, in the current study, all four methods are suitable for IL28B rs12979860 genotyping, but the ZNA assay can be a reliable tool. Due to its lower LD for SNP identification, this method is better than others for detecting this type of polymorphism.

Interleukin-28B TT genotype is frequently found in patients with hepatitis C virus cirrhosis but does not influence hepatocarcinogenesis.

Persistent hepatitis C virus (HCV) infection is associated with progressive hepatic fibrosis and ultimately hepatocellular carcinoma. The interleukin-28B (IL28B) rs12979860 polymorphism is associated with fibrosis progression in chronic HCV infection. IL28B encodes interferon-λ, which has both antiviral and anti-proliferative properties. This study aimed to determine whether IL28B rs12979860 polymorphism is also associated with development of hepatocellular carcinoma both in chronic HCV infection and in non-viral-related cirrhosis. Real-time polymerase chain reaction and melting curve analyses were used to genotype 311 patients who underwent liver transplantation for HCV cirrhosis (n=202) or alcoholic cirrhosis (n=109). HCV patients were older (p=0.012) and less likely males (p<0.001) than patients with alcoholic cirrhosis. IL28B rs12979860 TT genotype [OR 6.08, 95% CI 2.11-17.53; p<0.001] and T allele carriage (CT+TT; OR 2.3, CI 95% 1.42-3.72; p=0.001) were more frequent among HCV patients and, among them, more common in patients infected with HCV genotype 1 (CT+TT; OR 1.79, CI 95% 1.03-3.09; p=0.009). Incidence of hepatocellular carcinoma was higher in HCV cirrhosis (OR 2.7, CI 95% 1.5-4.7; p<0.001), with no differences according to HCV genotype. IL28B genotype distribution was similar among patients with or without hepatocellular carcinoma, in both HCV patients regardless viral genotype (p=0.84) and alcoholic patients (p=0.91). Multivariate analysis showed that older age (OR 1.06, CI 95% 1.02-1.1; p=0.003) and male gender (OR 2.49, CI 95% 1.24-5; p=0.01) were independent risk factors for hepatocellular carcinoma in HCV patients. In summary, the current study did not find a significant association between IL28B rs12979860 polymorphism and hepatocarcinogenesis.

Association of IL28B Polymorphism with Fibrosis, Liver Inflammation, Gender Respective Natural History of Hepatitis C Virus in Egyptian Patients with Genotype 4

The polymorphism of interleukin 28B (IL28B) rs12979860 is associated with spontaneous and treatment-induced clearance in hepatitis C virus (HCV) genotype 4 (G4). However, there is no information on its interaction with gender, moreover its association with intrahepatic inflammation in North Africans is not studied and its association with fibrosis in North Africans (especially Egyptians) is controversial. This study aims to explore the association between the minor allele of the IL28B rs12979860 polymorphism with gender, fibrosis and necroinflammation in Egyptian G4 HCV patients. IL28B rs12979860 was genotyped in 224 individuals, including 100 healthy controls and 124 consecutive patients with chronic HCV. Results showed (1) IL28B rs12979860 minor alleles associated with susceptibity to chronic HCV mainly in men not women, (2) no association between IL28B rs12979860 with fibrosis and necroinflammation activity, (3) the IL28B rs12979860 TT genotype associated with severe fibrosis in women only and with the necroinflammation activity in men using a recessive model. In conclusion, the IL28B rs12979860 polymorphism is not associated with fibrosis and liver inflammation in Egyptian HCV G4. Nonetheless, the TT genotype of IL28B rs12979860 polymorphism affects the natural history of each gender independently.

The predictive value of IL28B rs12979860, rs11881222 and rs8099917 polymorphisms and IP-10 in the therapeutic response of Egyptian genotype 4 patients

Interleukin-28B (IL28B) polymorphisms have previously been reported to be strongly associated with spontaneous and treatment-induced HCV viral clearance. AimTo assess the impact of four different IL28B polymorphisms and their haplotype combination and interferon-c inducible protein 10 (IP-10) in response to treatment in Egyptian genotype 4 patients. Method159 HCV-genotype 4 patients were included. All patients were treated with Peginterferon alph2a/Ribavirin for 48 wk. The following polymorphisms rs12979860, rs11881222, rs8103142 and rs8099917 and rs80803142 of Il-28 were known to be associated with the sustained virological response. They were genotyped using the TaqMan assay. IP-10 was assessed by Eliza. ResultsThe data indicated that all SNPs are within the Hardy-Weinberg Equilibrium (HWE) except for rs8103142 (p=6.255−9), therefore it was excluded from the study since it deviates from HWE-P. The CC, AA and TT genotypes of rs12979860, rs11881222 and rs8099917 were the more frequent genotypes among the responders at RVR, EVR, ETR and SVR, respectively. The frequency of CC, CT, and TT genotype was 46.4%, 38.1% and 15.5% among responders of RVR, and was 46.9%, 45.9% and 7.2 among responders of SVR for rs12979860, respectively. The relapse rate was 18.0% and 16.0 % during EVR and ETR, while the response rate was 52.8%, 58.5%, 59.7% and 61.6% after 4, 12, 48 and 72 weeks of treatment. The transient virological response (TVR) was 6.9% among HCV patients. The results showed that the odds ratio and 95% CI of HCV genotype 4 patients to have a better sustained response to treatment (SVR) was 2.92, (1.83–4.68, p=2.01−5), 2.89 (1.79–4.70, p=2.53−5), and 2.73 (0.21–0.65, p=0.0007) for those with the major allele “C” of rs12979860, the “A” allele of rs11881222, and the “T” allele of rs8099917, respectively. Furthermore, the positive predictive value (PPV) of the major homozygous alleles for SVR with better response to therapy was in the following order: 78.69%, 68.42%, and 32.14% with a positive likelihood ratio of 1.95, 1.25, and 0.86 for rs12979860, rs11881222 and rs8099917, respectively. The haplotype formed between the 3 studied SNPs (rs12979860, rs11881222 and rs8099917) showed that two haplotypes (TGG and TGT) increased the probability of a poor response to therapy, but the CAT haplotype had the opposite effect. Multinomial logistic regression analysis revealed that the viral load and rs12979860 are the only significant actors involved in the efficacy of the treatment response among the cohort study. In addition, patients with SVR had significantly lower values of IP-10 than non-responder patients (NR), with a P-value<=0.001. ConclusionsIn genotype 4 cases, the IL28B SNPs rs12979860 rs8099917, and rs11881222 are the strongest predictors of a response, while IP-10 is a strong negative biomarker of a response. Accounting for this factor is important in the individualization of treatment and enhances the degree of predictiveness of the IL28 polymorphism in the final treatment outcome. The frequent distribution of C, A and T alleles of IL28 polymorphism are higher among TVR, which may reflect sensitivity to prolonged course.

Impact of interleukin 28B polymorphisms on spontaneous clearance of hepatitis C virus infection: A meta‐analysis

Recent studies suggested that interleukin 28B (IL28B) polymorphisms may affect spontaneous clearance (SC) of hepatitis C virus (HCV) infection. Our purpose was to update the meta-analysis to reevaluate the impact of IL28B rs12979860 and rs8099917 polymorphisms on SC in patients infected with HCV. We searched PubMed, Web of Science, and Embase up to February 2013. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated by fixed- or random-effects models. Heterogeneity, sensitivity analysis, and publication bias were also assessed. Seventeen eligible papers were involved in this study. The SC rate was higher in patients with the rs12979860 CC (vs CT/TT OR = 2.98, 95% CI 2.53-3.50) and rs8099917 TT (vs GT/GG OR = 2.80, 95% CI 2.23-3.51) in the IL28B polymorphisms. Ethnicity stratification revealed that rs12979860 CC was associated with SC for Caucasians (vs CT/TT OR = 3.05, 95% CI 2.67-3.49), Asians (vs CT/TT OR = 1.88, 95% CI 1.33-2.66), and Africans (vs CT/TT OR = 3.15, 95% CI 2.39-4.15); rs8099917 TT was associated with SC for Caucasians (vs GT/GG OR = 2.48, 95% CI 1.96-3.15). IL28B rs12979860 and rs8099917 single nucleotide polymorphisms are significantly associated with SC of HCV infection. The predictive value of rs12979860 CC was stronger in Caucasians and Africans than in Asians.

Lack of evidence to support the association of a single IL28B genotype SNP rs12979860 with the HTLV-1 clinical outcomes and proviral load

BackgroundThe Interleukin 28B (IL28B) rs12979860 polymorphisms was recently reported to be associated with the human T-cell leukemia virus type 1 (HTLV-1) proviral load (PvL) and the development of the HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP).MethodsIn an attempt to examine this hypothesis, we assessed the association of the rs12979860 genotypes with HTLV-1 PvL levels and clinical status in 112 unrelated Brazilian subjects (81 HTLV-1 asymptomatic carriers, 24 individuals with HAM/TSP and 7 with Adult T cell Leukemia/Lymphoma (ATLL)).ResultsAll 112 samples were successfully genotyped and their PvLs compared. Neither the homozygote TT nor the heterozygote CT mutations nor the combination genotypes (TT/CT) were associated with a greater PvL. We also observed no significant difference in allele distribution between asymptomatic carriers and patients with HTLV-1 associated HAM/TSP.ConclusionsOur study failed to support the previously reported positive association between the IL28B rs12979860 polymorphisms and an increased risk of developing HAM/TSP in the Brazilian population.

Variation of interleukin-28B at rs12979860 in injection drug users with HCV infection in a Chinese population

Background: Hepatitis C virus (HCV) infection is a leading cause of liver disease globally. Recently, several genome-wide association studies have reported the strong association between single nucleotide polymorphisms (SNPs) near the interleukin-28B (IL28B) gene and the treatment outcome for chronic HCV infection. In Hong Kong, needle-sharing in injection drug users (IDU) continues to be a major route of HCV transmission. We conducted a follow-up study on HCV RNA-positive IDU to determine the genotype frequency of a SNP upstream of IL28B and their association with HCV genotype. Methods: A total of 273 IDU positive for anti-HCV and HCV RNA were included. Genomic DNA was extracted from whole blood samples, and the most strongly associated SNP near the IL28 gene, rs12979860, was determined by real-time PCR using a custom TaqMan genotyping kit. Results: The rs12979860 genotype distribution was CC in 237 IDU (86.8%), CT in 35 IDU (12.8%), and one case (0.4%) with TT genotype. The distribution of rs12979860 genotypes in the IDU population was in Hardy-Weinberg equilibrium (P = 0.810). Variation in the IL28B genotypes was not observed as compared with 300 healthy blood donors (CC: 87.0%, CT: 11.7%, and TT: 1.3%; P = 0.430). With regard to HCV genotype, HCV 1b and HCV 6a were the two commonest genotypes circulating in our local IDU population. Of the 105 IDU infected with HCV genotype 1 and 145 IDU with genotype 6, the frequency of the rs12979860 CC genotype was 81.9% and 88.3%, respectively, which were not different significantly (P = 0.509). Conclusion: In conclusion, the favorable rs12979860 CC genotype frequently observed in our Chinese population supports a potential role of incorporating IL28B SNP genotyping for the clinical workup of patients infected with HCV genotypes 1 and 6. Integrating the assessment of host and viral factors (age, gender, and HCV genotype) in combination with pre-treatment screening of IL28B rs12979860 polymorphism may provide useful prognostic information prior to interferon-based combination therapy for chronic HCV infection. This combined assessment may facilitate the development of new therapeutic approaches for the non-responders to conventional HCV therapies.

IL28B rs12979860 polymorphism does not influence outcomes of hepatitis B virus infection

rs12979860 in interleukin 28B (IL28B) gene is associated with response to interferon-α therapy and natural viral clearance in hepatitis C. The role of this polymorphism is less known in hepatitis B virus (HBV) infection. We evaluated whether rs12979860 was associated with outcomes of HBV infection. There were 651 individuals with persistent infection (387 with liver cirrhosis, 264 without cirrhosis) and 226 healthy individuals who recovered from HBV infection. The genotypic distributions were compared between different phenotypes pertaining to disease progression and HBV markers. The polymorphism had no association with clearance of hepatitis B surface antigen and hepatitis B e antigen, HBV-DNA level, apparent hepatitis onset and liver cirrhosis (P > 0.05). These results suggest that rs12979860 does not have such a strong effect in hepatitis B compared to hepatitis C.