FcγRIIa and Fcγ RIIIa genes polymorphism in Egyptian children with primary immune thrombocytopenia

Abstract Introduction Phagocytosis of autoantibody-sensitized coated platelets through Fc gamma receptors on phagocytic cells is an important mechanism of thrombocytopenia in primary immune thrombocytopenia (ITP). Objective We aimed to investigate the contribution of the FcγRIIa and FcγRIIIa genes polymorphism to the risk of ITP and their association with disease characteristics in Egyptian children. Methods A case control study was conducted on eighty children with primary ITP and eighty age and sex healthy matched subjects as a control group. The FcγRIIa and FcγRIIIa genes polymorphism was detected using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results We found that the FcγRIIa‐131H and ‐131R allele frequencies were 51.3 % and 48.7%, respectively, in children with ITP, versus 75% and 25%, respectively, in controls (p= 0.002). The compound heterozygous HR genotype was significantly higher in ITP patients (p < 0.05). The FcγRIIIa-158F and ‐158V allele frequencies were 46.3% and 53.7%, respectively, in children with ITP, versus 70% and 30%, respectively, in controls (p= 0.002). The compound heterozygous VF genotype was significantly higher in ITP patients (p < 0.05). The combined HR/FV genotype was 47.5% in ITP patients, versus 10% in controls (p < 0.001). No significant difference was found between children with newly diagnosed ITP and those who developed chronic ITP, regarding the frequency distribution of the FcγRIIa and FcγRIIIa alleles and genotypes (p > 0.05). Conclusion There is a possible association of the FcγRIIa and FcγRIIIa genes polymorphism with the risk for, and genetic susceptibility to ITP in Egyptian children, but large-scale studies are still needed to support our findings.

Clinical significance of p27 Kip1 expression in advanced ovarian cancer

Background: Ovarian cancer is the most common gynecological malignancy. In patients with advanced ovarian cancer, some biological parameters have prognostic implementations. P27kip1 is an inhibitor of a cycline-dependent kinase, its loss, can contribute to tumor progression. Objective: This study aimed to examine the importance of P27KIP1 protein in predicting the prognosis and response to neoadjuvant chemotherapy in patients with advanced ovarian epithelial cancer and to compare the outcomes of immunohistochemistry with Quantitative Real-time PCR. Patients and methods: We have studied P27KIP1expression by both immunohistochemistry and Quantitative Realtime PCR from 88 patients with advanced ovarian carcinomas undergone radical debulking surgery and received Paclitaxel followed by Cisplatin every 3 weeks for a total of 6 cycles. We also studied their association with both chemotherapy response and patient survival. Results: Nuclear expression of p27KIP1 protein was intense in 86 normal ovarian tissues and 42 of 88 carcinomas. The P27kip1mRNA expression level by qRT-PCR was very low in ovarian cancer tissues relative to its adjacent normal tissues. The results were statistically significant by both methods of determination. p27KIP1 expression was significantly related to good prognostic parameters as low stage tumors, differentiated tumors, absence of ascites, residual disease < 2 cm, and response to chemotherapy but not with histopathological type in case of determination by immunohistochemistry. Comparison of P27kip1 by both immunohistochemistry and qRTPCR with different prognostic parameters revealed no significant difference between both methods in the assessment of these parameters. In 4 years of follow-up, 20.5% of patients were alive without evidence of disease. 6.8% were alive with disease. The disease-related four -year survival rate for the whole group was 28.2%. In multivariate analysis, residual disease, histological type, tumor differentiation, ascites was of independent prognostic significance. Conclusion: In ovarian cancer, patients with loss of p27KIP1 expression are at a greater likelihood of disease progression, p27KIP1 may be used as a molecular marker to predict response to chemotherapy and prognosis. Both immunohistochemistry and qRT-PCR have equal reliability in the determination of p27 KIP1

Possible Relationship between Matrix Metalloproteinases Genotyping and Risk of Hepatocellular Carcinoma in HCV Infected Patients.

Background: The annual number of new cases of hepatocellular carcinoma (HCC) worldwide is over 1 million. In developing countries, the major cause of HCC is chronic hepatitis C virus (HCV) infection. Various studies have reported an association between functional gene polymorphism of matrix metalloproteinases (MMP) promoters and different cancers. Rationale: This study examined the association between MMP1 -1607, MMP9-1562, MMP14-6727 and MMP14-6767 gene polymorphisms and risk of HCC in HCV infected patients. Methods: The study enrolled 160 HCC patients, 91 with & 69 without chronic HCV infection, and 140 healthy subjects as control group. Genomic DNA was analysed for MMPs gene polymorphism using restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) for MMP1 and MMP9 but real time PCR was used for MMP14 genotyping. Results: MMP1-2G allele carriers had higher susceptibility of developing HCC in HCV infected patients. MMP9-1562 T/T genotype had high risk of developing HCC in HCV and non HCV related patients when compared to healthy controls. A significant lower risk for HCC was shown in individuals with MMP14-6767 G/A. The distribution frequency of MMP14-6767 G and MMP14-6727 C allele and homozygote genotype was significantly higher in HCC patients. Conclusion: MMP-1 -1607 2G allele carriers would alter the risk of HCC under specific conditions such as chronic infection with HCV. People with MMP9-1562 T/T genotype are at risk of developing HCC. MMP14-6767 G and MMP14-6727 C allele carriers and homozygote genotype might contribute to the prediction of susceptibility and pathological development of HCC in HCV infected patients.