Role of miR-146a rs2910164 and UTS2 rs228648 Genetic Variants in Behçet's Disease.

BACKGROUND: Behçet's disease (BD) is a chronic autoimmune inflammatory disease. Clinical studies revealed that both microRNAs and urotensin II (UTS2) play a significant role in the development of autoinflammatory diseases. PURPOSE: The study aimed to determine the association between miR-146a rs2910164 and UTS2 rs228648 genetic variants and BD susceptibility. In addition, the relationship between these gene variants and clinical and laboratory outcomes among Egyptian patients was investigated. METHODS: The distributions of miR-146a rs2910164 and UTS2 rs228648 (p.Thr21Met) variants were analyzed in 94 patients with BD and 115 healthy control subjects using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Taqman Real-time PCR techniques. RESULTS: Frequencies of the G/G genotype and G allele of miR-146a rs2910164 variant were significantly higher in patients with BD compared with normal controls (p = .042, OR = 2.31; p = .022, OR = 1.58, respectively). The frequencies of the Thr/Thr genotype and the Thr allele of UTS2 rs228648 variant were significantly higher in subjects with BD compared with normal controls (p = .028, OR = 3.35; p = .032, OR = 1.60, respectively). CONCLUSION: Our results suggest that miR-146a rs2910164 and UTS2 rs228648 variants have significant roles in both the development and clinical modulation of BD in Egyptian patients.

Circulating miRNA-122, miRNA-199a, and miRNA-16 as Biomarkers for Early Detection of Hepatocellular Carcinoma in Egyptian Patients with Chronic Hepatitis C Virus Infection.

BACKGROUND: Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world. Having a very poor prognosis, it currently ranks as the third most common cause of cancer-related deaths. MiRNAs are a set of small, single-stranded, non-coding RNA molecules that negatively regulate gene expression at the post-transcriptional level. Several miRNAs were found to be frequently deregulated in HCC. OBJECTIVE: To investigate whether miRNA-122, miRNA-199a, and miRNA-16 are altered in sera of hepatitis C virus (HCV)-induced HCC patients compared with chronic HCV patients without HCC, and to assess their diagnostic value to differentiate between HCC and chronic HCV in order to develop a non-invasive diagnostic and prognostic tool for HCC. METHODS: We analysed the expression of mature miRNA-122, miRNA-199a, and miRNA-16 in serum by a singleplex TaqMan two-step stem loop quantitative real-time reverse-transcription PCR (qRT-PCR) in 40 newly diagnosed HCC patients and 40 chronic HCV liver cirrhosis patients, as well as 20 apparently healthy individuals as a control group, using RNU48 as a normalisation control. RESULTS: Serum miR-16 was significantly lower in HCC than in HCV patients (P = 0.033). The serum level of miR-199a in chronic HCV patients was significantly lower than in healthy controls (P = 0.001). Receiver operating curve (ROC) analysis for serum miRNA-16 for discriminating HCC from HCV patients showed that at the cut-off value of 0.904, the sensitivity and specificity for this marker were 57.5 and 70 %, respectively. The combination of serum miR-16 with serum alpha fetoprotein (AFP) resulted in improved sensitivity to 85% and increased diagnostic accuracy to 87.5 %. Serum miR-199a and miR-16 were significantly associated with several parameters of HCC such as tumour size and number. CONCLUSION: The combination of serum miR-16 and serum AFP is a significant improvement on the current best practice of serum AFP for HCC in HCVpositive patients. Serum miR-199a and miR-16 could be used as potential indicators of the progress of HCC.