Role of ApoB-516C/T promoter gene polymorphism in the risk of Hepatitis C virus infection in Egyptian patients and in gender susceptibility.

At least 1 in 10 of the Egyptian population aged 15-59 is burdened with hepatitis C virus (HCV) infection, stamping Egypt the highest country harboring HCV worldwide. Considerable evidence supported the involvement of host genetic factors in the pathogenesis of HCV and the possibility of implementation in target therapies. ApoB gene polymorphisms are postulated to affect the susceptibility of HCV infection. Hence, we aimed to evaluate the relationship between ApoB-516C/T promoter gene polymorphism and HCV infection in a cohort of Egyptian patients and to explore whether higher levels of low-density lipoprotein (LDL) might compete with lipoviral particles (LVP) in the binding to LDL receptor (LDLR), thus escaping infection. Ninety-seven HCV patients and 96 matched controls were enrolled in this study. We genotyped ApoB-516C/T using PCR-RFLP method. ApoB concentrations were measured by immunoturbidimetric assay. The genotype and the allele frequencies of ApoB-516C/T promoter gene polymorphism in cases were statistically insignificant compared with healthy individuals (P = 0.109, 0.125, respectively). Sex stratification showed significantly lower counts of C/T genotype in female patients compared with female controls (P = 0.011, OR = 0.132, 95% CI = 0.026-0.657). Significantly higher levels of LDL and ApoB were detected in the control group (P < 0.001). This study shows that the ApoB-516C/T promoter gene polymorphism has no impact on the risk of HCV infection. However, the C/T genotype may be a protective factor for our female cohort. Further studies with larger samples are needed to verify this genetic gender diversity. Additionally, high levels of LDL and ApoB might prevent HCV infection.

Significant association between FasL gene -844T/C polymorphism and risk to hepatocellular carcinoma in Egyptian patients.

Fas/Fas ligand (FasL) system is the most critical apoptotic signaling entity in the extrinsic apoptotic pathway; hence mutations affecting this pathway may prevent the immune system from the removal of newly-formed tumor cells, and thus lead to tumor formation. The present study investigated the association between the FasL -844T/C polymorphism and the risk of hepatocellular carcinoma (HCC) in a cohort of Egyptian patients and explored the relationship of various clinical and pathological parameters with this single nucleotide polymorphism (SNP). Blood samples were withdrawn from hundred HCC patients and 100 age-, sex- and ethnically matched controls. The FasL -844T/C (rs763110) gene polymorphism was typed from genomic DNA using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. Genotype distributions and allelic frequencies between patients and control subjects showed that the TT homozygous patients were two times more likely to develop HCC (p=0.011). Also, the T allele was found to be a significant risk factor for the disease (OR 1.970, 95% CI 1.250-3.105, p=0.003). No association was detected between different parameters of the disease and the SNP. For the first time, our results suggest that the -844T/C polymorphism in the FasL gene confers risk to HCC. The alarming increase in the incidence of HCC in Egypt encourages further studies to document our results in a larger sample, and recommends more genetic studies hoping to define a genomic risk prediction specific to this cancer in our population.

Reversion-Inducing-Cysteine-Rich Protein With Kazal Motifs (RECK) Gene Single Nucleotide Polymorphism With Hepatocellular Carcinoma: A Case-Control Study.

BACKGROUND: The reversion-inducing-cysteine-rich protein with kazal motifs (RECK) gene is a transformation suppressor gene that can negatively regulate matrix metalloproteinases (MMPs) and inhibit tumor invasion, angiogenesis, and metastasis. So, the aim of this study was to analyze the effect of RECK gene rs 11788747 single nucleotide polymorphism (SNP) on hepatocellular carcinoma (HCC) susceptibility and its relation to various clinical and laboratory data of the patients. METHODS: This is a case-control study including 200 HCC patients and 200 healthy controls. RECK rs 11788747 genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: RECK rs 11788747 A/G and G/G genotypes frequencies were significantly higher in HCC patients compared to the healthy controls. The HCC patients possessing at least one polymorphic G allele were significantly at a higher risk of developing lymph nodes involvement and distant metastasis. CONCLUSION: This study revealed the role of RECK rs 11788747 SNP in HCC in Egyptian patients, which consequently might be used as a prognostic tool and could be added to its therapeutic strategies.