Mervat Khorshied

PTPN22 1858C>T gene polymorphism has been associated with several autoimmune disorders including alopecia areata. The aim of the current study was to investigate the effect of the inherited genetic polymorphism 1858C>T of PTPN22 gene on the predisposition to severe forms of alopecia areata and its effect on the response to DPC treatment. To achieve our aim, PTPN22 1858C>T genotyping was performed by PCR-based restricted fragment length polymorphism (PCR-RFLP) analysis. The study included 103 Egyptian patients with extensive alopecia areata treated by DPC. Hundred healthy age and sex matched blood donors were included in the current study as a control group. Results of genotyping showed that PTPN22 CT and TT mutant genotypes were significantly higher in AA patients compared to controls and conferred increase risk of AA (OR = 2.601, 95% CI = 1.081–6.255). Statistical comparison between AA patients with wild and mutant genotypes revealed that the duration of the illness was significantly longer in those harboring the mutant genotypes. Moreover, the association of other autoimmune diseases as atopy and diabetes mellitus was higher in patients with mutant genotypes. Furthermore, PTPN22 1858C>T genetic polymorphism did not affect the patients' response to DPC immunotherapy.

Hepatitis C virus (HCV) has been postulated to be an etiological agent for lymphoid malignancies. Polymorphisms in oxidative stress genes as; superoxide dismutase (SOD2), glutathione peroxidase (GPX1), catalase (CAT), myeloperoxidase (MPO) and nitric oxide synthase (NOS2) may influence non-Hodgkin’s lymphoma (NHL) risk. HCV screening and polymorphisms in these five genes coding for antioxidant enzymes were studied in 100 Egyptian patients with B cell-NHL and 100 controls to clarify the association between HCV infection, oxidative stress genes polymorphisms and B cell-NHL risk. A significantly higher prevalence of HCV infection was detected among NHL patients relative to controls and this carried a 14-fold increased NHL risk (odds ratio (OR) = 14.3, 95% confidence interval (CI) = 5.4–38.3, p < 0.0001). GPX1 and MPO genetic polymorphisms conveyed increase in B-NHL risk (OR = 3.3, 95% CI = 1.4–7.4, p = 0.004 and OR = 4.4, 95% CI = 1.3–14.2, p = 0.009 respectively). Further analyses stratified by HCV infection revealed that concomitant HCV infection and GPX1 gene polymorphism had a synergetic effect on NHL risk with an OR of 15 (95%CI = 2.2–69.6, p < 0.0001). In addition, combined HCV infection and MPO gene polymorphisms had a pronounced NHL risk (OR = 9.2, 95%CI = 2.5–33.9, p < 0.0001). SOD2, CAT and NOS2 genetic polymorphisms were not found to confer increased NHL risk. This study revealed that HCV infection is a risk factor for NHL in Egypt. Polymorphisms in GPX1 and MPO genes may influence NHL risk in HCV infected Egyptian patients. Larger scale studies are warranted to establish this genetic susceptibility for NHL.

Background and purpose: Non-Hodgkin lymphomas are closely related diseases with distinctive morphologic, immunophenotypic, genetic, and clinical features. Genetic susceptibility studies of NHL are mandatory to identify at risk populations and to clarify important disease mechanisms. Caspase genes play a key role in regulation of apoptotic cell death, and dysregulation of this signaling pathway has been shown to participate in tumorigenesis. The current study aimed at defining the role of Caspase 8-D302H, Caspase 8-652 6N ins/del and Caspase 10-I522L genetic polymorphisms as risk factors for NHL and their possible role as genetic prognostic markers.

Methods: The present study included 100 Egyptian B-cell NHL patients and 100 healthy controls. Genotyping of the studied genes was performed by polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) technique. Data was analyzed using SPSS statistical package version 15.

Results: The study revealed that CASP8-D302H mutant genotypes were significantly higher in NHL patients when compared to the controls and conferred increased risk of NHL. For CASP8-652 6N ins/del and Casp10- I522L, there was no statistical difference in the distribution of the different genotypes between NHL cases and the controls. Furthermore, there were no statistical differences between NHL patients harboring the wild or mutant genotypes of the studied genes as regards their response to therapy.

Conclusions: CASP8-D302H genetic polymorphism represents a genetic risk factor for NHL in Egyptian population. Hopefully, better understanding of the functional consequences of caspase genes polymorphism would provide a foundation for future studies of the possible role of these genes in lymphomagenesis.

The angiogenic-related factors: angiopoietin-1 and -2 and their receptor Tie-2 have wide-ranging effects on tumor behavior that includes angiogenesis and, inflammation. These multifaceted pathways present a potential target in developing novel inhibition strategies for cancer therapy. The present work aimed at detecting the prevalence of expression of: angiopoietin-1, angiopoietin-2, and their receptor Tie-2 in 56 Egyptian de novo acute myeloid leukemia (AML) patients by conventional RT-PCR to verify the prognostic impact of their expression on the response to induction chemotherapy. Thirty age- and sex-matched healthy volunteers were subjected to the same analysis as a control group. High expression of angiopoietin-1 (Ang-1) was detected in the patient group but not the control group. AML patients expressing angiopoietin-2 (Ang-2) either solely or in combination with high Ang-1 and/or Tie-2 showed unfavorable response to induction chemotherapy; either failed induction or death during induction. These data provide evidence that the alternation of angiopoietin balance in favor of Ang-2 may play a critical role in the pathophysiology of AML. Furthermore, positive pre-therapeutic expression of Ang-2 indicates valiable unfavorable prognostic marker in AML patients and may be used as a prognostic tool in the risk-adaptive management of AML.

Genetic polymorphism within the regulatory regions of tumor necrosis factor-alpha (TNF-α) and Lymphotoxin-alpha (LT-α) may be involved in the development of lymphoid malignancies. The aim of the current study was to investigate the effect of TNFα−308 and LTα+252 genetic polymorphism on susceptibility to non-Hodgkin lymphoma (NHL) in Egypt. Genotyping of the studied genes by restriction fragment length polymorphism polymerase chain reaction was conducted on 84 NHL and 100 healthy controls and revealed that TNFα−308 homotype (AA) was significantly higher in NHL patients and conferred sixfold increased risk of NHL (OR = 5.9, 95%CI = 2.3–16.1). Moreover, TNFα/LTα high-producer haplotypes were significantly higher in NHL patients and conferred increased risk of NHL (OR = 4.59, 95%CI = 2.19–9.42).