Impact of Apo E gene polymorphism on HCV therapy related outcome in a cohort of HCV Egyptian patients.

The functional apolipoprotein E (Apo E) gene polymorphism could be used as a determinant of outcome of HCV infection. This study aimed to demonstrate the impact of Apo E genotype on the response to HCV combined therapy. MATERIAL AND METHODS: The study has been implemented on 125 individuals with persistent HCV infection and 120 cases with sustained virologic response (SVR). All participants were genotyped for ApoE gene polymorphism by a real-time quantitative PCR (qPCR). RESULTS: Statistically significant differences were demonstrated regarding the Apo E genotypes between the two groups (P-value < .001) where the frequency of E3E3 was significantly higher among the chronic HCV-patients while E3E4 and E4E4 genotypes frequencies were higher among the SVR-subjects group and E3E3 genotype was associated with increased risk of chronicity (OR 4.7; 95% CI 1.9-12.1, P-value < .001). Moreover, There were statically significant differences regarding E3 and E4 alleles frequencies, where E3 allele display a higher frequency among the chronic HCV-patient group while the SVR-subjects group showed higher frequency of E4 allele and the carriers of E3 allele have 1.4 times more risk to develop chronicity than those with E4 allele (OR 1.4; 95% CI 1.0-2.0, P-value < .05). Meanwhile the protective E2 allele was absent in all infected participants. CONCLUSION: This study supports the hypothesis of the protective impact of Apo E4 allele that favors viral clearance of HCV infection and its recovery after combined therapy, while the Apo E3 allele is considered as a particular risk factor for the chronicity in HCV patients and resistance to therapy. Whereas the Apo E2 allele confers a resistance to HCV infection at a time of exposure.

Interactive Effects of Immunoglobulin Gamma and Human Leucocyte Antigen Genotypes on Response to Interferon Based Therapy of Hepatitis C Virus.

AIM: We examined the role that immunoglobulin GM 23 and KM allotypes-genetic markers of γ and κ chains, respectively-play in response to treatment of hepatitis C virus (HCV) infection in Egyptian patients. MATERIAL AND METHODS: A total of 120 persons who had responded to HCV treatment and 125 with persistent HCV infection were genotyped for the presence of GM23 and KM determinants. HLA -C genotyping was also done. RESULTS: Association of GM 23+ and KM3 was significantly associated with non response to treatment (P < 0.0001). Individuals who lacked this GM genotype (but were positive for KM1,2 and 3) were likely to respond to treatment (P=0.045). Association of heterozygous GM23 (+/-) with KM 1,2 and 3 or KM3 alone was significantly associated with SVR (P = 0.001) and (P = 0.0001) respectively. Particular combinations of HLA and GM genotypes were associated significantly with the response to HCV treatment. The combination of HLAC2C2 and GM23+ was associated with persistence of infection (P = 0.027) while the association of HLAC2C2 and heterozygous GM23+/- was associated with SVR (P = 0.001). The association of HLAC1C1 and heterozygous GM23+/- was significantly associated with SVR (P = 0.001) and also subjects with HLA C1/C2 and heterozygous GM23+/- were likely to respond to treatment (P = 0.003) while subjects with HLA C1/C2 and GM23+ show tendency to resist to treatment (P = 0.0001). CONCLUSION: Our results didn't support a role for KM allotypes, GM23 allotype plays a role in the persistence of HCV infection in the presence or absence of KM1,3. Interaction between certain GM and HLA-C genotypes may favor adequate response to interferon based therapies.

Serum levels of interleukin-8, tumor necrosis factor-α and γ-interferon in Egyptian psoriatic patients and correlation with disease severity.

Psoriatic plaques have been shown to contain increased levels of pro-inflammatory cytokines. Also, serum levels of several cytokines have been reported elevated in psoriatic patients. It is postulated that changes in cytokine production both locally and systemically could be useful in monitoring disease activity. The aim of this study was to evaluate serum cytokine profile of interleukin (IL)-8, γ-interferon (IFN-γ) and tumor necrosis factor-α (TNF-α) in Egyptian psoriatic patients by enzyme-linked immunosorbent assay (ELISA) technique and to correlate these levels with disease severity. We analyzed serum samples from 60 Egyptian patients (31 females and 29 males) with a mean age of 40.2 ± 17.4 years with active psoriasis, and 21 healthy volunteers for major T-helper type 1 cytokines using the ELISA technique. The disease severity, including erythema, induration and scales, was assessed by Psoriasis Area and Severity Index (PASI) score. TNF-α and IFN-γ were markedly elevated in all sera from psoriatic patients. TNF-α was found a more efficient predictor for disease severity than IL-8 and IFN-γ using three receiver-operator curves with accuracy. IL-8 was also moderately elevated and correlated with the age of patients (r = 0.28). We have obtained evidence that TNF-α in our study was found to be more useful than the other two tested cytokines, IL-8 and IFN-γ as a follow-up marker for monitoring disease severity in Egyptian psoriatic patients. A positive correlation between lL-8 and the age of the patients was also noted.

Relationship between codon 249 mutation in exon 7 of p53 gene and diagnosis of hepatocellular carcinoma.

INTRODUCTION: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Multiple genetic and epigenetic changes are involved in the molecular pathogenesis of HCC. Heat shock proteins have essential roles in protecting cells from the potentially lethal effects of stress. Among them, HSP70 are often overexpressed in cells of various cancers and have been suggested to contribute to tumourigenesis. p53 mutations in codon 249 have also been identified in HCC. MATERIAL AND METHODS: Fifty patients with liver disease were enrolled in this study compared to 10 healthy volunteers. The studied patients were divided into 2 groups: group I includes those suffering from HCC, group II includes those suffering from post-hepatitis B and C liver cirrhosis. The presence of p53 gene mutation was detected by DNA extraction from whole blood of patients and controls followed by polymerase chain reaction then restriction fragment length polymorphism (RFLP) analysis of codon 249 of exon 7. We also studied the genotypes of the HSP70 gene by PCR followed by RFLP analysis. RESULTS: Our results revealed no statistical difference between group I, group II, and the control group as regards exon 7 mutation of the p53 gene. Also the frequency of polymorphic genotypes of HSP70 showed no significant difference between the 3 studied groups. CONCLUSIONS: The present study supports the view that the incidence of point mutation of p53 codon 249 mutations in exon 7 of the p53 gene may not play a role in carcinogenesis of HCC in Egyptian patients. Also, genetic polymorphism in HSP70 was not associated with high risk of future development of HCC.