FAS and FAS-Ligand Promoter Polymorphisms in Hepatitis B Virus Infection

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.