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Infections with hepatitis B virus (HBV) may lead to a distinct clinical outcome which is partially related to host genetic variability. Our aim was to investigate the relationships between the polymorphisms of the E-selectin gene and disease progression in a HBV-infected Chinese Han population, and also to determine the plasma soluble E-selectin (sE-selectin) levels in this population.Genomic DNA was extracted from the peripheral blood of 367 HBV carriers and 281 healthy controls. Two polymorphisms (PstI for A561C and HphI for G98T) of the E-selectin gene were analyzed by polymerase chain reaction-restriction fragment length polymorphism. Circulating sE-selectin levels were measured by specific enzyme-linked immuno-sorbent assay (ELISA).The frequency of the C allele (AC or CC) of the A561C polymorphism was significantly higher in patients with liver cirrhosis (LC) compared to controls (p=0.002). There was no difference in allele distribution of the G98T polymorphism. But in patients with LC, classified according to the Child-Pugh classification, the frequency of the T carrier (GT and TT) was significantly different between Child-Pugh class A and class B plus C (p=0.009). Levels of plasma soluble E-selectin (sE-selectin) were significantly increased in HBV carriers with chronic hepatitis (CH) and LC (mean±SD 68.94±34.09 and 43.39±18.00 ng/mL) compared to controls (13.96±7.50 ng/mL) (p<0.01). In the LC subgroup, levels of sE-selectin were significantly decreased from Child-Pugh class A to class C (p<0.05). In each group, individuals with the C allele showed higher sE-selectin levels than those with the A allele (p<0.05).This is the first report describing the association between E-selectin polymorphisms and HBV-related chronic liver diseases. Our data suggest that the A561C polymorphism of the E-selectin gene may be associated with disease progression in patients with chronic HBV infection and control the expression of plasma soluble levels, while the G98T polymorphism may be related to fibrotic severity in the Chinese population.