Correlation between a single nucleotide polymorphism (G/T at nt –88) in the Mx1 gene promoter and the response to interferon therapy for hepatitis C virus in Egyptian patients (original) (raw)
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African Journal of …, 2011
Interferon used in the treatment of hepatitis C virus (HCV) patients stimulates the expression of a number of host genes encoding enzymes with antiviral activities, including myxovirus resistance gene-1 (Mx1). Mx1 gene was found to have a single nucleotide polymorphism (SNP) at position -88 in the promotor region that affect the expression of Mx 1 protein and was suggested to be associated with the response of HCV. In this study, we assessed the relation between the SNP in the Mx1 gene and the responsiveness of Egyptian HCV patients to pegylated interferon and ribavirin treatment along with other host-related and virus-related predictors of treatment outcome. We genotyped the biallelic G/T SNP in the promoter region of Mx1 gene at position -88 from the transcription start site by restriction fragment length polymorphism (RFLP) in 42 interferon treatment-naïve Egyptian patients that were treated with pegylated interferon and ribavirin. We found that Mx1 nt-88 SNP is not significantly correlated to achieving sustained virological response (SVR) after pegylated interferon alpha and ribavirin combined treatment. We conclude that Mx1 gene polymorphism at codon nt-88 cannot be considered as biological marker to potentially identify responders and non-responders of HCV patients to achieve a sustained virological response to treatment with interferon (IFN) in combination with ribavirin.
Gastroenterology Research, 2017
Background: Pegylated interferon (PegIFN) is used in the treatment of chronic hepatitis C virus (HCV) patients especially in resource limited countries. Treatment with PegIFN stimulates the expression of a number of host genes encoding enzymes with antiviral activities, including myxovirus resistance gene-A (MxA gene). MxA gene was found to have a single nucleotide polymorphism (SNP) at position-88 in the promoter region that affects the expression of MxA gene protein and was suggested to affect the treatment outcome. The aim of the work was to assess the relation between the SNP in the MxA gene and its impact on treatment of chronic HCV patients with PegIFN and ribavirin. Methods: We therefore genotyped the biallelic G/T SNP in the promoter region of MxA gene at position-88 from the transcription start site by restriction fragment length polymorphism (RFLP) in 70 chronic HCV genotype 4 interferon naive Egyptians and 40 healthy controls. Results: G allele was the prevalent one in both HCV patients group (105, 74.5%) and control group (66, 82.5%), while T allele was less expressed in patients group (36, 25.5%) and control group (14, 17.5%). There is no correlation between genotypes and response to IFN-alpha therapy:
MxA expression as marker for assessing the therapeutic response in HCV genotype 4 Egyptian patients
Journal of Viral Hepatitis, 2010
The prevalence of hepatitis C virus (HCV) infection varies across the world, with the highest number of infections reported in Egypt. Expression of the MxA gene has been found to be a reliable and sensitive marker for the induction of endogenous type I interferons (IFNs) during viral infections. This study examined the correlation of gene expression of MxA with the response to treatment with pegylated-IFN-alfa2b and ribavirin. Fifty patients with type 4 HCV and 20 healthy volunteers as controls were enrolled in a prospective study designed with strict inclusion criteria to nullify the effect of confounding variables and further minimize selection bias. Quantification of HCV-RNA and MxA gene by real-time PCR was performed for every patient, and quantification of MxA gene was performed for controls. There was a statistically significant difference between patients and control group as regards the quantity of MxA gene expression (P < 0.05) (Mann-Whitney test) (P = 0.004). There was a statistically significant difference between responders and nonresponders (P < 0.05): responders showed a higher percentage of cases with initial MxA <2 6 (P < 0.05). We conclude that MxA protein expression is a sensitive biological marker for ongoing virus replication and presence of type 1 IFN. These results highlight the importance of the detection of MxA expression at the start of therapy as a factor for assessing the likelihood of HCV genotype 4 patients to achieving a sustained virological response to treatment with IFN-a2 in combination with ribavirin.
Genes and Immunity, 2003
Interferon stimulates the expression of a number of genes encoding enzymes with antiviral activities, including myxovirus resistance-1 (MxA), 2-5-oligoadenylate synthetase 1 (OAS-1) and double-stranded RNA-dependent protein kinase (PKR). We examined whether polymorphisms in these genes influenced the outcome of hepatitis C virus (HCV) infection. We observed a lower frequency of the GG genotype at position À88 in the MxA gene promoter in self-limiting HCV infection (OR ¼ 0.56; 95% CI: 0.35-0.8; P ¼ 0.010) and in nonresponders to therapy (OR ¼ 0.49; 95% CI: 0.25-0.95; P ¼ 0.020). This genotype predominantly influenced the outcome of treatment in patients with viral genotype 1 (OR ¼ 0.22 95% CI: 0.07-0.67; P ¼ 0.002). A polymorphism in the 3 0-untranslated region of the OAS-1 gene was associated with outcome of infection (GG genotype less frequent in self-limiting infection: OR ¼ 0.43; 95% CI: 0.21-0.86; P ¼ 0.010). A polymorphism at position À168 in the promoter region of the PKR gene was associated with self-limiting infection (CT genotype: OR ¼ 2.75; 95% CI: 1.45-5.24; P ¼ 0.002). Further associations were found with a CGG trinucleotide repeat in the 5 0 UTR region of the PKR gene. Polymorphisms in the interferon-induced genes, MxA, OAS-1 and PKR appear thus associated with HCV outcome.
Antiviral Research, 2005
To investigate the influence of the T-to-A polymorphic sequence at position +874 in the interferon (IFN)-␥ gene (+874 IFN-␥) on the response to combination therapy with high-dose interferon and ribavirin, the single nucleotide polymorphisms were determined by using a polymerase chain reaction sequence-specific primers approach in 150 histologically proved chronic hepatitis C (CHC) patients. The distribution of genotypes for +874 IFN-␥ were T/T: 6 (4.0%), T/A: 31 (20.7%) and A/A: 113 (75.3%) and 24.7% (37/150) of patients were inherited T allele. After undergoing combination therapy with high-dose IFN-␣ and ribavirin, 70.7% (106/150) of patients achieved sustained viral response (SVR). Based on multivariate regression analyses, the independent factors predicting HCV SVR after combination therapy were HCV genotype non-1b (P < 0.001) and low pretreatment HCV RNA levels (P = 0.041) (odds ratios/95% C.I.: 10.150/4.023-25.609 and 0.581/0.345-0.979, respectively). No association between genotypes, A or T alleles of +874 IFN-␥ and response to combination therapy with high-dose IFN-␣ and ribavirin.
Hepatitis monthly, 2014
Hepatitis C virus (HCV) infection as a worldwide health problem is associated with cirrhosis and hepatocellular carcinoma. With current treatment regimen, pegylated interferon (PEG-IFN) plus ribavirin, sustain virological response (SVR) is achieved in only 50% of infected individuals. In HCV infection, an inappropriate ratio of cytokines may affect the benefit of antiviral therapy. Given the polymorphisms in regulatory regions of cytokines genes may influence cytokines production. We aimed to investigate both the frequency of genotypes and alleles of interferon gamma (IFN-γ) gene at +874A/T, +2109A/G, and -183G/T loci in HCV-infected patients and their associations with response to therapy. A total of 158 patients were included and treated with PEG-IFN plus ribavirin. The presence of HCV infection in patients was confirmed by reverse transcription polymerase chain reaction, and genomic DNA was extracted from peripheral leukocytes using salting out method. IFN-γ gene polymorphisms we...
Hepatology, 2009
Combination treatment with pegylated-interferon-α and ribavirin, the current recommended therapy for chronic hepatitis C virus (HCV) infection, results in a sustained virological response (SVR) in only about half of patients. Because genes involved in the interferon-α pathway may affect anti-viral responses, we analyzed the relationship between variants in these genes and SVR among participants in the HALT-C trial. Patients had advanced chronic hepatitis C and had previously failed to respond to interferon-based treatment. Participants were treated with peginterferon-α2a and ribavirin during the trial. Subjects with undetectable HCV RNA at week 72 were considered to have had an SVR. Subjects with detectable HCV RNA at week 20 were considered non-responders. We used TaqMan assays to genotype 56 polymorphisms found in 13 genes in the interferon-α pathway. This analysis compares genotypes for participants with an SVR to non-responders. The primary analysis was restricted to European American participants because a priori statistical power was low among the small number (n=131) of African American patients. We used logistic regression to control the effect of other variables that are associated with treatment response. Among 581 European American patients, SVR was associated with IFNAR1 IVS1-22G (adjusted odds ratio [aOR], 0.57; p=0.02); IFNAR2 Ex2-33C (aOR, 2.09; p=0.02); JAK1 IVS22+112T (aOR, 1.66; p=0.04); and ADAR Ex9+14A (aOR, 1.67; p=0.03). For the TYK2 -2256A promoter region variant a borderline association was present among European American participants (OR, 1.51; p=0.05) and a strong relationship among African American patients; all 10 with SVR who were genotyped for TYK2-2256 carried the A variant compared to 68/120 (57%) non-responders (p=0.006). In conclusion, genetic polymorphisms in the interferon-α pathway may affect responses to antiviral therapy of chronic hepatitis C. Welzel et al.
Human Immunology, 2012
Osteopontin (OPN) is an extracellular matrix glycophosphoprotein produced by several types of cells including the immune system. The present study examined the possibility that single-nucleotide polymorphisms (SNP) in the promoter region of the OPN at nt À443 is a marker predicting the therapeutic efficacy of pegylated interferon (peg-IFN-a2b)-ribavirin combination therapy in Egyptian patients with chronic hepatitis C. Blood was collected from 95 patients with chronic hepatitis C who had received peg-IFN-a2b-ribavirin combination therapy and 100 age and sex matched controls. SNP in OPN at nucleotide (nt) À443 and its serum protein level were analyzed. Sustained virological response (SVR) was higher in patients with T/T at nt À443 than in those with C/C or C/T. A univariate logistic regression analysis showed that fibrosis grade, serum OPN protein level and T/T homozygotes of SNP at À443 were significant predictors for response. Receiver operating characteristics (ROC) analysis revealed the diagnostic and prognostic efficacy of serum OPN. It can be concluded that SNP in the promoter region of OPN at nt À443 and serum OPN protein level are predictors of response to the efficacy of peg-IFN-a2b-ribavirin therapy in Egyptian patients with chronic hepatitis C. Ó