Digging more in the genetic risk prediction of hepatitis C virus epidemic in Egypt: Apoptosis genes polymorphisms in the susceptibility of hepatitis C virus and association with viral load.

Egypt is confronted with the highest hepatitis C virus (HCV) epidemic. Apoptosis and cellular immune responses are crucial to the clearance or persistence of viral infections. This case-control study was carried out to detect whether apoptosis genes single nucleotide polymorphisms (SNPs) confer risk to HCV in a cohort of Egyptian patients and to explore their association with viral load. One hundred and ninety six blood samples were withdrawn from 96 HCV patients and 100 controls. The Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) -1525G>A and FasL-844T>C SNPs were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Hepatitis C viral load was measured using Real time PCR. Results Genotypes distributions of TRAIL -1525G>A and FasL-844 T>C polymorphisms in controls were in accordance with Hardy-Weinberg equilibrium (p>0.05). The study showed a statistically significant difference in the distribution of the TRAIL -1525G>A polymorphism genotypes and the FasL-844 T>C polymorphism genotypes between the HCV patients and the controls (p=0.001 and 0.02 respectively), with association of the -1525GA genotype and -844 TT genotype with increased risk of HCV infection (OR=2.68, 1.942 respectively, 95% CI=1.482-4.846, 1.1-3.43, respectively). No significant association was detected between TRAIL, FasL and the viral load. Our results suggest that the FasL -844T>C SNP is implicated in the susceptibility to HCV in Egyptian patients and firstly report the involvement of TRAIL gene polymorphism in the risk of the disease. Therefore we recommend national programs to delineate genetic factors that may put individuals at risk for contracting HCV.

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.

Study of serum syndecan-1 levels in a group of Egyptian juvenile systemic lupus erythematosus patients.

The aim of the study was to assess the serum levels of Syndecan-1 in a group of Egyptian juvenile systemic lupus erythematosus (JSLE) patients and to study any possible associations with disease activity, renal activity and organ damage. Serum level of Syndecan-1 was assessed in 60 Egyptian JSLE patients and 30 apparently healthy age and gender matched children using ELISA. SLE Disease Activity Index-2000 (SLEDAI-2K), renal SLEDAI-2K, renal activity score and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index were assessed for all patients. Serum SDC-1 levels were higher in patients with JSLE than in healthy controls (p<0.001) and were positively correlated with SLEDAI-2K (p<0.001), with renal SLEDAI score (p=0.008) and renal activity score (p=0.04). So, Syndecan-1 might be used as a marker for disease activity and renal activity in JSLE patients.

Contribution of Toll-Like Receptor 9 Gene Single-Nucleotide Polymorphism to Systemic Lupus Erythematosus in Egyptian Patients.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease, with multiple genetic and environmental factors involved in its etiology. The toll-like receptor 9 (TLR9) gene has been reported to have important roles in the development and progression of SLE. In this case-control study, the effect of TLR9 polymorphism on susceptibility to SLE was investigated in Egyptian patients. METHODS: We studied the distribution of the TLR9 rs352139 (G + 1174A) single nucleotide polymorphism (SNP) by allele-specific polymerase chain reaction (PCR) in 104 Egyptian patients with SLE and 108 age-, sex-, and ethnically matched controls. RESULTS: There was no statistically significant difference in the distribution of the AA genotype and alleles between SLE patients and the control group in our study; however, the GA heterozygous patients were three times more likely to develop SLE (P < 0.001). A significant association was detected between TLR9 genotypes and some of the disease manifestations as myositis (p = 0.032), psychosis (p = 0.014), photosensitivity (p = 0.002), and pleurisy (p = <0.001). Moreover, we observed a significant association between the TLR9 AA and GA genotypes and the presence of antinuclear antibodies (ANA) (p = 0.038). CONCLUSION: The G + 1174A SNP in the toll receptor 9 gene may contribute to the genetic susceptibility of SLE in Egyptian patients. Also, an influence for this polymorphism on disease manifestations has been elucidated.

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.

A Study of VEGF Gene Polymorphism in Egyptian Patients with Diabetic Retinopathy.

BACKGROUND: There are subgroups of patients with diabetes mellitus (DM) in whom diabetic retinopathy (DR) does not develop despite poor long-term control of their disease, while others exercising fairly good control, develop retinopathy. So, we aimed to investigate the association of DR with -2578 polymorphism of the vascular endothelial growth factor (VEGF) gene, which has been reported to be associated with increased VEGF production, in Egyptian diabetic patients. MATERIALS AND METHODS: This is a case control study in which 148 diabetic patients were enrolled. Among them, 44 subjects had proliferative diabetic retinopathy (PDR), 30 had non-proliferative diabetic retinopathy (NPDR), and 74 individuals without retinopathy served as controls. A single nucleotide polymorphism (SNP) of the VEGF gene, a C→A transversion at -2578 (the C/A polymorphism), was investigated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: We found a higher frequency of the polymorphic genotype in both the NPDR (66.7%) and PDR (72.7%) groups compared to the wild C/C genotype (33.3% in NPDR and 27.3% in PDR), but with no statistically significant difference from the control group. Significant association of the progression of DR to the polymorphic genotype was achieved at diabetes duration more than 20 years. CONCLUSION: Despite of the higher frequency of both the polymorphic genotype and the A allele in cases with DR compared to the control group, there might be no significant association between the VEGF gene polymorphism and DR per se, unless it is longstanding.

Susceptibility and progression of end stage renal disease are not associated with angiotensin II type 1 receptor gene polymorphism.

CONTEXT: The role of the angiotensin II type 1 receptor (AT1R) gene polymorphism, A1166C, has been shown to be associated with end stage renal disease (ESRD) and its progression. There is also some evidence that HLA class II alleles are associated with ESRD independent of other factors. OBJECTIVE: To examine the association between AT1R gene polymorphism in the susceptibility and progression to ESRD in patients with chronic renal failure and to investigate if the AT1R genotypes and HLA-DR alleles predict the time to ESRD. MATERIALS AND METHODS: Genotyping was performed in 50 ESRD patients and 44 control subjects for the AT1R A1166C gene polymorphism using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). ESRD patients were examined for HLA-DRB1 alleles according to a reverse hybridization line probe assay. RESULTS: Allele and genotype frequencies of the AT1R polymorphism did not differ significantly between ESRD patients and controls. Furthermore, there was no association between the AT1R gene polymorphism or HLA-DRB1 alleles with the time to the occurrence of end stage failure. DISCUSSION AND CONCLUSION: We concluded that the AT1R genotype does not contribute to the genetic susceptibility of ESRD and is not associated with progression of chronic kidney failure to ESRD.

TRAIL mRNA expression in peripheral blood mononuclear cells of Egyptian SLE patients.

Although the definite etiopathogenesis of systemic lupus erythematosus (SLE) remains unclear, many different mechanisms may contribute to its pathogenesis. Tumor-necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor (TNF) family with pro-apoptotic activity. The accumulation of apoptotic cell debris has been hypothesized to induce the autoimmune inflammation in SLE, and TRAIL may trigger this programmed cell death. We investigated TRAIL mRNA expression levels in peripheral blood mononuclear cells (PBMCs) from 60 SLE patients and 40 controls using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR), and we studied the association between the results and clinical and laboratory parameters of the patients. Expression levels of TRAIL mRNAs in SLE patients were significantly higher than in controls (p<0.001). A statistically significant association was detected between TRAIL mRNA expression and SLE activity (p=0.001).