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.