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A Programmed Cell Death‐1 Haplotype is Associated with Clearance of Hepatitis B Virus

Purpose. Programmed cell death 1 (PD‐1) is an important immune checkpoint of T cells response and plays a critical role in chronic hepatitis B virus (HBV) infection. The purpose of this study was to investigate the associations between PD‐1 polymorphisms and susceptibility and disease progression of chronic HBV infection. Methods. In this case‐control study, 299 cases with chronic HBV infection comprised of 99 asymptomatic carriers (ASCs), 96 patients with chronic hepatitis B (CHB), and 104 patients with HBV‐related acute on chronic liver failure (HBV‐ACLF) were enrolled. A total of 82 spontaneously recovered subjects were enrolled as controls. Three single nucleotide polymorphisms (SNPs) of PD‐1, including PD‐1.1, PD‐1.5, and PD‐1.9 were analyzed by Sequenom MassARRAY system. Results. The frequency of PD1.1 AA genotype was found to be significantly higher in the chronic HBV infection group compared with spontaneously recovered group (27.1% vs. 18.3%, P=0.049), and the frequency of PD‐1.5 TT genotype and allele T were both significantly lower in chronic HBV infection group compared with spontaneously recovered group (genotype: 4.7% vs. 9.8%, P=0.04; allele: 22.1% vs. 30.5%, P=0.025). The frequency of haplotype GTC (PD‐1.1 G, PD‐1.5 T, PD‐1.9 C) was significantly lower in patients with chronic HBV infection compared with spontaneous recovery cases (P=0.026). No significant differences were found in the genotype distributions of the three SNPs among the different clinical types of chronic HBV infection (P>0.53). Conclusions. Our results suggest that PD1 polymorphisms are associated with susceptibility to chronic HBV infection in the Chinese population. Future studies with larger sample sizes and different ethnic populations are required to validate our findings.