Association between miRNA-146a and Polymorphisms of its Target Gene, IRAK1, Regarding Susceptibility to and Clinical Features of Systemic Lupus Erythematous and Multiple Sclerosis.

Single-nucleotide polymorphisms (SNPs) in microRNA-146a (miRNA-146a) can be associated with the development of immune-system dysfunctions.The aim of this work is to correlate SNPs of miRNA-146a and its target gene, IRAK1, with susceptibility, clinical manifestations, and diseases progression in patients with systemic lupus erythematous (SLE) and multiple sclerosis (MS). Genotyping for miRNA-146a (rs2910164) and its target gene IRAK1 (rs3027898) was performed using real-time polymerase chain reaction (RT-PCR) in 80 patients with SLE and 70 patients with MS, as well as 120 healthy control individuals. A statistically significant difference was found between the frequencies of the genotypes and alleles of miRNA-146a (rs2910164) and IRAK1 (rs3027898), compared with the control group. Also, whereas the mutant allele G of miRNA-146a may be a factor in the pathogenesis of lupus nephritis, the mutant allele C of IRAK1 may play a role in lupus arthritis. Both genes may contribute to the susceptibility of patients to SLE and MS.

Role of circulating miR-182 and miR-150 as biomarkers for cirrhosis and hepatocellular carcinoma post HCV infection in Egyptian patients.

In Egypt, liver diseases are exceptionally high, maintaining the highest prevalence of hepatitis C virus (HCV) worldwide, and increasing rates of hepatocellular carcinoma (HCC). Available diagnostic methods show poor performance in early diagnosis of HCC. Definite pathogenic factors contributing in the development of HCV are still lacking. MicroRNAs have been reported as promising biomarkers for cancers diagnosis and in virus-host interaction. This study was conducted to detect the role of miR-182 and miR-150 as biomarkers for development of cirrhosis and malignant transformation in HCV infected patients. The expression of miR-182 and miR-150 was evaluated using real-time quantitative PCR (qRT-PCR) in 120 subjects: 40 HCC patients, 40 hepatitis C patients (20 cirrhotic and 20 non-cirrhotic HCV genotype 4) and 40 healthy controls. In HCC, statistically significant decrease of miR-182 and miR-150 compared to non-cirrhotic HCV patients (p = 0.015, p = 0.006 respectively) and of miR-150 compared to controls (p = 0.039). In cirrhotic HCV patients, significant down regulation of miR-182 and miR-150 compared to non-cirrhotic HCV (p = 0.003, p = 0.024 respectively). On the other hand, significant upregulation of miR-182 was observed in non-cirrhotic HCV compared to controls (p = 0.036). Alpha-fetoprotein (AFP) showed sensitivity 15% for HCC diagnosis at the cut-off value of 400 ng/ml, while combining AFP with miR-182 and miR-150, resulted in improving sensitivity to (90%) and diagnostic accuracy to (80%). miR-182 and miR-150 can be used as non invasive biomarkers for HCC and combination of these miRNAs and AFP markedly improve the diagnosis of HCC. Both miR-182 and miR-150 can also be used as predictive markers for detection of cirrhosis progression in HCV infected patients.

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.