Background: The FAS and FAS-Ligand (FASL) system is an important apoptosis pathway in the liver. The FAS-mediated pathway functions by binding the FASL on the activated cytotoxic T lymphocytes and Natural Killer (NK) cells to the FAS receptor on infected hepatocytes. FAS and FASL polymorphisms, which are related to apoptosis, might influence the outcome of Hepatitis B Virus (HBV) infection.Objectives: Thus, the present study aimed to determine if FAS and FASL promoter polymorphisms are associated with the clinical outcome of HBV infection.Patients and Methods: DNA samples were obtained from the infected individuals including chronic carrier (n = 50), chronic hepatitis (n = 50), cirrhosis (n = 25), naturally recovered (n = 26) and compared with those of their matched healthy controls (n = 100). Genotyping for polymorphisms of FAS-670 A/G and -1377 G/A, and FASL -844 C/T was performed using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assays.Results: Multiple analyses for genetic association of FAS and FASL polymorphisms were not statistically different between HBV patients (n = 125) and healthy controls (n = 100). However, genotype and allele frequencies of FASL-844 C/T were significantly different between recovered individuals and patients with cirrhosis (P = 0.02 and P=0.01, respectively). Whereas, FAS-670A/G and -1377G/A polymorphisms were similarly distributed in these two groups (P = 0.8 and P = 0.47, respectively).Conclusions: The current study results showed that bearing -844T allele in FASL promoter region has a protective effect on cirrhosis and is involved in recovery from infection. In conclusion, it is proposed that HBV infection outcome might be influenced by FASL-844C/T polymorphism through alteration in apoptosis of hepatocytes.

Regulation of normal cell growth and turnover is balanced between cell proliferation, cell differentiation and apoptosis.A disruption of this balance is thought to be an important event leading to carcinogenesis One of the effectors molecules in apoptosis is FAS antigen. Cross linking of FAS by its ligand (FAS L) or agonistic anti FAS antibodies induces apoptosis of cells expressing FAS on the membrane by triggering cascade of caspaces. The aim of this research was to study the percent of expression of FAS antigen on bone marrow and peripheral blood cells in 100 patients suffering from acute lymphoid and myeloid leukemia by flow cytometry method. Sample was obtained at the time of diagnosis before antileukemic therapy. Expression of FAS antigen on normal control peripheral leukocytes was also analysed.From these data, it was found that FAS antigen is expressed in all cases, but the expression level varied widely.The percentage of FAS antigen expression in all of acute lymphoid leukemia samples was below 20%, but in acute myeloid leukemia samples, 8 out of 50 cases was above 20%. In normal control samples, the mean value for monocytes was higher than granulocytes and in granulocytes higher than lymphcytes.Expression of FAS antigen in most of the leukemic cells was low and the preliminary results showed that increase in FAS antigen expression above 20% after treatment, is a favorable prognostic sign associated with increase relapse free and total survival. Thus evaluation of this antigen before, during and after treatment is recommended.

Background: The precise responsible mechanism of pre-eclampsia remains controversial however, recent data suggest a main role of the abnormal activation of the adaptive immune system and Apoptosis. In this study, we have measured serum levels of FAS/FASl as two important members of extrinsic apoptotic pathway in patient with pre-eclampsia. Methods: 207 participants including 99 pre-eclampsia patients and 108 age and sex-matched normal pregnant women were involved in the case-control study. Plasma sample from each participant was collected and stored at –, 20 ̊, C until batch processing. Serum levels of FAS and FAS ligand were measured by ELISA for each participant including 99 pre-eclampsia patients and 108 normal pregnant women. Following a test of statistical normality, nonparametric data were analyzed by Mann-Whitney. Results: sFAS levels in case group was significantly higher than controls,584 (397-892) pg/ml in cases opposed to 341 (213-602) pg/ml in controls (p value< 0. 01). sFASL in pre-eclampsia women was a little lower than controls,255 (173-318) pg/ml and in case group compared to 265. 5 (184-381. 5) pg/ml in controls. Conclusions: We have found the increased levels of sFAS in patients with pre-eclampsia in compare with the healthy pregnant women. It seems that abnormality in sFAS is related with pre-eclampsia.

Background: The FAS/FAS ligand (FASL) system has been recognized as an important pathway for apoptosis induction in cells and tissues. It has recently been shown that skin lesions of pemphigus vulgaris are associated with FAS mediated apoptosis. The aim of this study was to evaluate the level of serum soluble FAS of ten newly diagnosed patients with pemphigus vulgaris.Methods: Sera were collected from ten patients with pemphigus vulgaris.Commercial sandwich enzyme-linked immunosorbent assay (ELISA) for quantitative detection of soluble FAS was applied.Results: Patients with mucosal skin involvement had higher median values in contrast to patients with cutaneous involvement.Conclusion: Elevation of soluble FAS in our study may give insights for the pathogenesis of pemphigus vulgaris. Suppression of this underlying mechanism may be an important target for novel therapies and relapse prevention.

Background: The FAS receptor/ligand system including soluble forms is the most important apoptotic initiator in the liver. Dysregulation of this pathway may contribute to abnormal cell proliferation and cell death and is regarded as one of the mechanisms preventing the immune system from rejecting the tumor cells.Objectives: To analyze the role of FAS system FAS/ FAS ligand (FAS/ FASL) in the multi-step process of hepatic fibrosis/carcinogenesis, and to use of the serum markers as possible candidate biomarkers for early detection of hepatocellular carcinoma (HCC).Patients and Methods: Ninety patients were enrolled: 30 cases of chronic hepatitis C (CHC) without cirrhosis, 30 cases of CHC with liver cirrhosis, and 30 cases of HCC and hepatitis V virus (HCV) infection. Ten wedge liver biopsies, taken during laparoscopic cholecystectomy, were served as normal controls. Serum soluble FAS (sFAS) levels were measured using ELISA technique; FAS and FASL proteins were detected in hepatic tissue by indirect Immuno-histochemical technique (IHC); electron microscopic (EM) and immune electron microscopic examinations were performed for detection of FAS expression on lymphocytes.Results: Hepatic expression of both FAS and FASL as well as expression of FAS on separated lymphocytes were significantly increased in the diseased groups (P<0.01) compared to the control specimens. The highest expression was noticed in CHC specimens, particularly with the necro-inflammatory activity and advancement of the fibrosis. The sFAS in cirrhotic patients and HCC were significantly higher than that in normal controls and CHC without cirrhosis group (P<0.01).Conclusions: Apoptosis and the FAS system were significantly involved in the process of converting liver cirrhosis into hepatocellular carcinoma. Down-regulation of FAS expression, up regulation of FASL expression in hepatocytes, and elevation of serum sFAS levels were important in tumor evasion from immune surveillance, and in hepatic carcinogenesis.

Background: The First apoptosis signal (FAS) and First apoptosis signal ligand (FASL) genes initiate the apoptosis pathway, playing a central role in the tumor growth and metastasis. Gene polymorphisms including-1377 G/A in the promoter region of FAS and-844 C/T in the promoter region of FASL have shown to change the transcription activities of these genes. Methods: In this study we evaluated association of these polymorphisms with risk of metastasis of breast cancer, in a population selected from Mashhad, Iran. A total of 115 patients with breast cancer and 115 controls were recruited in this case-control study. Polymerase Chain Reaction-based Restriction Fragment Length Polymorphism (PCR-RFLP) was applied for genotyping on extracted DNA from participant’ s blood. Unconditional logistic regression was used to estimate cancer risk by calculating odds ratios (OR) and their 95% confidence intervals (95% CIs). Results: There was no significant association between these genetic polymorphisms and breast cancer risk. Additionally, our results showed no significant influence from the above mentioned gene polymorphisms on metastasis of breast cancer. Conclusions: These results suggest that the FAS-1377G/A and FASL-844 C/T gene polymorphism don’ t have much influence on the susceptibility to metastasis of breast cancer in northeastern Iranian population. Therefore, we suggest to investigate impact of other candidate gene polymorphisms on metastasis of breast cancer for future research.