Impact of genetic polymorphisms of four cytokine [G] genes on treatment induced viral clearance in HCV infected Egyptian patients

Background: Many factors contribute for viral clearance and response to antiviral therapy. Genetic polymorphisms of cytokines, chemokines, and their receptors can alter the immune response against Hepatitis C virus [HCV]

Aim of the study: The aim of the current study is to assess single nucleotide polymorphism [SNP] in the promoter region of IL-10, TNF-alpha, IFN-y and TGF-p as predictors of response to combined Pegylated interferon ot/ribavirin [PEG-IFN/RBV] therapy in chronic HCV infected Egyptian patients

Patients and methods: The study was conducted on 150 HCV infected patients and 100 apparently healthy control subjects. All patients were treated with PEG-IFN/RBV. They were classified according to their icsponse to treatment

Genotyping of IL-10, TNF-alpha, IFN-y and TGF-p were performed on peripheral blood DNA using polymerase chain reaction-restriction fragment-length polymorphism [PCR-RFLP] and primer specific assays

Results: Overall, 83/150 [55.3%] patients achieved sustained virological response [SVR], whereas 67 [44.7%] did not. Age and BMI were significantly lower in patients who achieved SVR [P < 0.05]. IL-10 at site [-1082] GG genotype was associated with SVR where odds ratio was 1.98 with 95% confidence interval [1.34-3.65]

None of the other genes showed a significant association with SVR

Conclusion: Analysis of IL-10 SNP at promoter site [-1082] could be used as a pretreatment predictor of response to combined PEG-IFN/RBV treatment

Circulating MiRNA-21 and programed cell death [PDCD] 4 gene expression in hepatocellular carcinoma [HCC] in Egyptian patients

Background: Circulating microRNAs [miRNAs] are endogenous, small [17-25 nucleo-tides] non-coding RNAs that are overexpressed in many human cancers including hepatocellular carcinoma [HCC]. Moreover, circulating miRNAs can reflect the level of tissue miRNAs, so could be potential tumor markers. miRNA-21 regulates post-transcriptional expression of tumor suppressor gene; programed cell death 4 [PDCD4] gene which implies that miRNA-21 might be a novel diagnostic and/or prognostic marker for cancer

Objective: To evaluate the diagnostic and prognostic potential of circulating miRNA-21 and study the expression of PDCD4 gene as a target of miRNA-21 in HCC in Egyptian patients

Subjects and methods: This study was conducted on 30 HCC patients, 20 chronic liver disease [CLD] patients due to HCV infection and 20 healthy subjects. Serum alpha fetoprotein [AFP] was measured for all participants. The relative plasma expression of each of miRNA-21 and PDCD4 gene was determined in whole blood samples using real-time polymerase chain reaction

Results: The results revealed over expression of miRNA-21 and under expression of PDCD4 gene in HCC group [p < 0.05] compared to both CLD and healthy subjects, while no significant change was detected between CLD and healthy subjects. miRNA-21 expression was negatively correlated with PDCD4 gene expression. miRNA-21 expression increased significantly with presence of cirrhosis, increased number of focal lesions, larger size of tumor, advanced tumor stage and presence of vascular invasion. Receiver Operator of Characteristics [ROC] curve analysis of plasma miRNA-21 revealed that, at a cut-off value of 3.93 [fold expression], the sensitivity and specificity for differentiation of HCC cases were 93% and 90%, respectively

Conclusion: Circulating miRNA-21 could be a novel early diagnostic and prognostic biomarker for detection of HCC. Approaches interfering with the miRNA-2 l/PDCD4-axis, or releasing PDCD4 expression, may have a strong basis for therapeutic uses in cancer in the future

Impact of IL28B polymorphism on treatment induced viral clearance in HCV infected Egyptian patients

Interleukin [IL] 28B single nucleotide polymorphisms [SNP] was recently recognized as predictor of SVR in HCV infected patients treated by combination therapy of pegylatedinterferon [Peg-IFN] and ribavirin [RBV]. The aim of the current study was to assess IL 28B polymorphism SNP [rs12979860] as a predictor of response to combined Peg-INF/RBV therapy in Egyptian chronic HCV infected patients. The study was conducted on 247 HCV infected patients and 100 apparently healthy control subjects. All patients were treated with PEG-IFN-alpha/ribavirin; and they were classified according to their response to treatment. Genotyping of IL28B rs12979860 was performed on peripheral blood DNA using polymerase chain reaction restriction fragment length polymorphism [PCR-RFLP] assay. The overall frequency of IL28B genotypes was 24.7%, 50.2% and 25.1% for genotypes CC, CT and TT respectively, while the response rate was 82%, 38.7% and 43.8% for genotypes CC, CT and TT respectively, moreover, genotype CC had increased probability to HCV clearance than both genotypes CT and TT with OR 7.71 [95%CI: 3.71-15.79]. Genotyping of IL28B at SNP rs12979860 could be used as a guide to tailor treatment in Egyptian patients infected with HCV for better outcome