Host genetic background is known as an important factor in patients’ susceptibility to infectious diseases such as viral hepatitis. The aim of this study was to determine the effect of genetic polymorphisms of interleukin-16 (IL-16) cytokine on susceptibility of hepatitis B virus (HBV) infected patients to develop chronic HBV infection. Genotyping was conducted using PCR followed by enzymatic digestion and RFLP (restriction fragment length polymorphism) analysis. We genotyped three single nucleotide polymorphisms (SNPs) in the Il-16 gene (rs11556218 T>G, rs4778889 T>C, and rs4072111 C>T) to test for relationship between variation at these loci and patients’ susceptibility to chronic HBV infection. Allele frequency of Il-16 gene rs4072111 and rs11556218 was significantly different between chronic HBV patients and healthy blood donors. Genotype frequency of rs4778889 polymorphism of Il-16 gene was significantly different when chronic HBV patients and HBV clearance subjects were compared. Our results showed that Il-16 gene polymorphisms are considerable host genetic factors when we chase biomarkers for prognosis of HBV infected patients. 1. Background and Objectives More than 350 million individuals around the world are infected with hepatitis B virus. The diagnosis of chronic infection is made by a combination of serology, viral, and biochemical markers [1]. Prevalence of anti-HBc and HBsAg in the United States at 2006 is estimated to be 4.7% and 0.27%, respectively [2]. Iran is located on intermediate endemic region for hepatitis B infection and prevalence of HBsAg positivity among general adult population in about 3 to 10 percent in different regions [3]. World Health Organization (WHO) and Center for Disease Control and Prevention (CDC) reported that prevalence of chronic hepatitis B infection in Iran ranges between 2 and 7 percent [4]. Occult HBV infection is reported among 7 to 13 percent of anti-HBc positive and/or anti-HBs positive subjects, but this type of viral hepatitis is seen in 0 to 17 percent of healthy blood donors. When we investigate the susceptibility factors for HBV clearance this phenomenon could have confounder effect. So HBV-DNA PCR test must be performed for all study subjects to obviate this issue [5]. Interleukin-16 (Il-16) is a multifunctional cytokine with the role of immune response synchronization and direction [6]. The mature secreted form of this protein acts as a ligand for CD4+ cells and this ligand-receptor binding leads to activation of a key intracellular pathway that regulates T cell proliferation [7]. The major Il-16
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