IL28B polymorphism does not determine outcomes of hepatitis B virus or HIV infection.
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ABSTRACT:
SUBMITTER: Martin MP
PROVIDER: S-EPMC2974014 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The aim of the study was to evaluate the serological rate of Helicobacter pylori (H. pylori) infection in patients with chronic hepatitis C virus (HCV) infection and determine any correlations with liver damage and IL28B single-nucleotide polymorphism (SNP). One hundred eighty-nine patients with chronic HCV infection were included in the study, and H. pylori status was defined based on anti-H. pylori-IgG or anti-CagA-IgG antibodies using enzyme-linked immunosorbent assay (ELISA). Liver damage was assessed using histology or transient elastography. IL28B C/T polymorphism (rs12979860) was evaluated in circulating blood cells using a PCR-based restriction fragment length polymorphism assay. Overall H. pylori serology was positive in 38.1% of our HCV-infected subjects. Among those, the anti-CagA-IgG positivity rate was 43.1% and was within the range of previously described populations of the same region. Highest prevalence of H. pylori was found in patients between 31 and 40 years compared to other age subgroups. The seropositivity rate was higher in the non-cirrhotic group than the cirrhotic one (45.4% vs. 20.0%, p < 0.05). No difference was found in IL28B genotype between H. pylori-positive and -negative cohorts. However, we observed a trend for the lower anti-CagA-IgG expression level in relation to the IL28B T-allele. Our results do not support an association between HCV and H. pylori infection. Whether IL28B SNP has a functional role in modulation of serological response to H. pylori CagA needs further investigation.
| S-EPMC5867570 | biostudies-literature
Project description:BACKGROUND:Interleukin (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. METHODS:Searched 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. RESULTS:Eighteen 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). CONCLUSION:IL28B 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.
| S-EPMC7195703 | biostudies-literature
Project description:Treatment-induced control and spontaneous clearance of hepatitis C virus (HCV) infection are affected by various host factors. Polymorphisms in the region of the gene IL28B are associated with HCV clearance, implicating the gene product, interferon (IFN)-?3, in the immune response to HCV. Although it is not clear how the IL28B haplotype affects HCV clearance, IFN-?3 up-regulates interferon-stimulated genes, similar to IFN-? and IFN-? but via a different receptor. There is also evidence that IFN-?3 affects the adaptive immune response. The IL28B genotype can be considered, along with other factors, in predicting patient responses to therapy with pegylated IFN-? and ribavirin. We review the genetic studies that uncovered the association between IL28B and HCV clearance, the biology of IFN-?3, the clinical implications of the genetic association, and areas of future research.
| S-EPMC3072961 | biostudies-literature
Project description:INTRODUCTION:To study the prevalence of hepatitis C virus (HCV) infection in blood donor (BD), haemodialysis (HD) and intravenous drug user (IVDU) populations in Singapore and assess the IL28B polymorphism if HCV positive. METHODS:The BD population were healthy volunteers, the HD population were patients who were on haemodialysis for at least six months of follow-up between January 2009 and December 2014. IVDU population was from inmates at halfway houses who consented. RESULTS:Between 2011 and 2014, of 161,658 individuals who underwent screening prior to blood donation, 95 (0.059%) were positive for HCV. Of the 42 sera available, common genotypes (GTs) were GT-3 (47.6%) and GT-1 (31.0%). Of 1,575 HD patients, 2.2% were anti-HCV positive. The HCV GT distribution was HCV GT-1 (32.4%), HCV GT-3 (20.5%) and GT-6 (8.8%). 83 halfway house inmates were screened. Of the 47 IVDUs, 36.2% were anti-HCV positive with predominant GT-3 (%). IL28B polymorphism was noted to be CC predominantly 85.3%. CONCLUSION:Prevalence of HCV infection has decreased in both the BD and HD populations. However, it remains high in the IVDU population. GT-1 remains the most common in the HD population; however, GT-3 infection is now more common among the BD population in Singapore. IL28B - CC is the predominant variant among the HCV-infected individuals in Singapore.
| S-EPMC6351688 | biostudies-literature
Project description:Single-nucleotide polymorphisms (SNPs) around IL28B are associated with spontaneous hepatitis C virus (HCV) clearance of genotypes 1 and 3 in white and African-American populations. This study investigated whether the IL28B SNP (rs12979860) is associated with spontaneous clearance of HCV, principally genotype 4, in 162 Egyptians (80 with clearance). The protective C allele was more common in those with spontaneous clearance (76.3% vs 57.9%; P = .0006). Individuals with clearance were 3.4 (95% confidence interval, 1.8-6.5) times more likely to have C/C genotype. Thus, IL28B plays a role in spontaneous clearance of HCV genotype 4 in North Africa.
| S-EPMC3182308 | biostudies-literature
Project description:Background/aimsSingle-nucleotide polymorphisms (SNPs) near the interleukin 28B gene (IL28B; interferon [IFN]-?-3) are associated with outcomes of chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infection treated with peginterferon (PEG-IFN) alpha-based antiviral therapy. In this study, we investigated the influence of IL28B polymorphisms on spontaneous clearance of HBV infection in a large Korean cohort.MethodsBetween January 2007 and June 2010, a total of 208 patients with chronic HBV infection and newly diagnosed HBV-related hepatocellular carcinoma were recruited as the CC group [HBsAg(+) for >6 months, anti-HBc(+), and anti-HBs(-)]. In addition, 351 organ donors were stratified into the UE group [n?=?106; HBsAg(-), anti-HBc(-), and anti-HBs(-)] or the SC group [n?=?245; HBsAg(-), anti-HBc(+), and anti-HBs(+)]. The SNaPshot ddNTP Primer Extension Kit (Applied Biosystems, Foster City, CA) was used for SNP detection. Direct full sequencing of the IL28B coding region was attempted.ResultsRegardless of group, rs12979860 CC was most frequently identified (85.0% in UE, 85.9% in SC, and 93.5% in CC, respectively), whereas rs12979860 TT was not identified in any group. Similarly, rs12980275 AA and rs8099917 TT were most frequently identified (?85%) regardless of group, whereas rs12980275 GG was identified in only one subject in the SC group. In addition, rs8099917 GG was not identified. The prevalences of CC in rs12979860, AA in rs12980275, and TT in rs8099917 were significantly higher in the CC group when compared with the UE and SC group (all P<0.05). Among 19 novel SNPs in the IL28B coding region, the proportions of 6 SNPs were significantly different among the UE, SC, and CC groups (all P<0.05).ConclusionsThe SNP upstream of IL28B that has the strongest genetic association with HCV recovery has an inverse influence on HBV recovery. Additional studies are needed to understand the mechanisms of this SNP in HBV infection.
| S-EPMC3714234 | biostudies-literature
Project description:AimsGenome-wide association studies highlighted single nucleotide polymorphisms (SNPs) within the IFNL3/IL28B locus predict the treatment outcome for patients with HCV. Furthermore, SNPs in newly discovered IFNL4 are shown to have population-specific correlation with spontaneous clearance of HCV. The aim of this study was to examine the prevalence and clinical significance of the outlined SNPs in a population from Central Asia, a multi-ethnic region with a developing economy and a high prevalence of HCV infection.MethodsOne hundred and thirty-five chronic HCV patients from Uzbekistan were enrolled. DNA specimens were extracted from peripheral blood mononuclear cells and the IFNL3 SNPs (rs8099917, rs12979860) were genotyped by the Invader Plus assay, the TaqMan assay, and by direct sequence analysis. The IFL4 region (ss469415590) was sequenced.ResultsOf the 135 patients that completed 24 or 48 weeks of treatment with Peg-IFN-? plus RBV, 87.4% were of Central Asian (CA) ancestry and 12.6% were of Eastern European (EE) ancestry. A non-virological response was observed in 21.2% of CA and in 35.3% of EE, respectively (p<0.32). The rs12979860 was strongly associated with treatment response (OR, 5.2; 95% CI, 1.9-14.6; p<0.004) in the overall sample; however, SNP rs8099917 was the most predictive of outcome for CA group (OR, 6.9; 95% CI, 2.6-18.0; p<0.002). The allele frequency of IFNL4 SNP, ss469415590, was identical with that of rs12979860 in all samples.ConclusionsSNPs in IFNL3 and IFNL4 can be used to predict HCV treatment outcome in a population of Central Asian ancestry.
| S-EPMC3963975 | biostudies-literature
Project description:Until recently, the standard treatment of chronic hepatitis C virus (HCV) infection was a combination therapy with PEG-IFN-? plus ribavirin. Previous studies have proven that several markers predict the outcome of such therapy, e.g., pretreatment plasma levels of interferon inducible protein IP-10, HCV RNA and IL28B-related single nucleotide polymorphisms (SNP). Altered activity of tryptophan metabolizing enzyme indoleamine 2,3-dioxygenase (IDO) has been also shown in patients suffering from HCV infection. In this study, we investigated whether IL28B SNP in patients infected with HCV is related to the tryptophan breakdown rate. Before therapy, serum tryptophan and kynurenine concentrations were determined in 25 patients with established HCV infection and the kynurenine to tryptophan ratio (KYN/TRP) was calculated as an estimate of the tryptophan breakdown rate. In parallel, neopterin and nitrite concentrations were determined. A significant difference of serum KYN/TRP existed between the three IL28B polymorphism groups: C/C genotype had the highest and T/T genotype had the lowest KYN/TRP (p < 0.05). Likewise, C/C genotype was associated with higher KYN/TRP than non-C/C genotype (p = 0.01). There was a smaller difference between the three groups regarding the absolute kynurenine concentrations, the C/C genotype being associated with higher kynurenine concentrations. None of the other comparisons revealed any statistical significance. In conclusion, patients with C/C genotype presented with the highest tryptophan breakdown rate already before antiretroviral therapy with IFN-?/ribavirin. The differences in tryptophan metabolism might relate to HCV clearance and also to side effects of IFN-? therapy.
| S-EPMC4491665 | biostudies-other
Project description:BACKGROUND:Genome-wide association studies have revealed several single-nucleotide polymorphisms around interleukin 28B (IL28B) that are strongly associated with hepatitis C virus (HCV) clearance. However, their predictive value is not perfect, which suggests that other genetic factors may also be involved in HCV clearance. We previously reported a wide variation in the length of a thymine-adenine (TA) dinucleotide repeat in the promoter region of IL28B and that the transcriptional activity of the promoter increased gradually in a TA repeat length-dependent manner. METHODS:We determined the length of the TA repeats of 1,060 Japanese and 201 African-American samples to investigate the relation to spontaneous HCV clearance. RESULTS:The distribution of the TA repeats greatly differed between the two ethnicities. The variation ranged from 10 to 18 repeats, and the most frequent allele, 12, accounted for over 80% for Japanese. The African-American data showed a gently sloping distribution, and the allele with six repeats was detected only in the African-American sample. The TA repeats 11 or greater were correlated with spontaneous clearance. Multiple logistic regression analysis extracted the genotype of the TA repeats as an independent factor in both the Japanese [p = 0.0004, odds ratio (OR) = 13.02 95% confidence interval (CI) = 2.59-237.0] and African-American (p = 0.027, OR = 3.70 95% CI = 1.16-11.8) populations. CONCLUSIONS:A long TA repeat in the promoter region of IL28B was associated with spontaneous HCV clearance. Although its efficacy may be limited in Japanese population because of its allele distribution, this novel genetic factor will be useful for predicting HCV clearance especially for the African Americans.
| S-EPMC4651429 | biostudies-literature
Project description:BACKGROUND/AIMS:Polymorphism at the IL28B gene may modify the course of hepatitis C virus (HCV) chronic infection. Our aim was to study the influence of IL28B rs12979860 gene polymorphism on the biochemistry and pathology of HCV-induced disease in the clinical course from mild chronic hepatitis C to hepatocellular carcinoma. METHODS:We have determined the rs12979860 single nucleotide polymorphism (SNP) upstream IL28B gene in two groups of patients with HCV-induced chronic liver disease: 1) 268 patients (159 men) with biopsy-proven chronic hepatitis C, to analyse its relation with biochemical, virological and histological features; and 2) 134 patients (97 men) with HCV-related hepatocellular carcinoma. The distribution of the analysed SNP in hepatocellular carcinoma patients was compared with that found in untreated chronic hepatitis C patients. All patients were white and most were Spaniards. RESULTS:In multivariate analysis ALT values were higher (P = 0.001) and GGT values were lower (P<0.001) in chronic hepatitis C patients homozygotes for the major rs12979860C allele as compared with carriers of the mutated rs12979860T allele. Steatosis was more frequent (Odds ratio = 1.764, 95% C.I. 1.053-2.955) and severe (P = 0.026) in carriers of the rs12979860T allele. No relation was found between the analysed SNP and METAVIR scores for necroinflammation and fibrosis, and there were no differences in the distribution of the analysed SNP between hepatocellular carcinoma and untreated chronic hepatitis C patients. CONCLUSION:The IL28B rs12979860 polymorphism correlates with the biochemical activity and the presence and severity of liver steatosis in chronic hepatitis C.
| S-EPMC3362530 | biostudies-literature