Association Between Hepatitis B Viral Burden in Chronic Infection and a Functional Single Nucleotide Polymorphism of the PDCD1 Gene

• DOI: 10.1007/s10875-010-9450-1
• Publication Date: 2010-08-10T11:42:10Z
• Authors: Linghua Zheng; Dongling Li; Fusheng Wang; Hao Wu; Xiaozhu Li; Junliang Fu; Xinyue Chen; Lizhong Wang; Yang Liu; Shengdian Wang
• Keywords: Adult; Male; 0301 basic medicine; Hepatitis B virus; Genotype; Virulence; DNA Mutational Analysis; Programmed Cell Death 1 Receptor; Middle Aged; Viral Load; Polymorphism, Single Nucleotide; Inteins; 3. Good health; 03 medical and health sciences; Hepatitis B, Chronic; Antigens, CD; Humans; Female; Apoptosis Regulatory Proteins; Genetic Association Studies

PD-1, encoded by PDCD1, is highly expressed on virus-specific T cells and plays critical roles in modulating anti-virus immune responses in chronic viral infection. It is unknown, however, whether polymorphisms of the PDCD1 are associated with viral clearance during chronic viral infections.Here, we used the polymerase chain reaction-restriction fragment length polymorphism method to genotype two single nucleotide polymorphisms (SNPs) of PDCD1 in 502 patients with chronic hepatitis B virus (HBV) infection and 359 healthy controls to determine the association between PDCD1 genotypes and serum viral load as well as the risk of chronic infection. Our results showed that although neither the P7209(C/T) SNP site nor the P8737(A/G) site was associated with the risk of chronic HBV infection, the P7209 (T) allele in intron 4 is significantly associated with lower viral burden in the blood. Using a luciferase reporter assay, we demonstrated that the P7209 (T) allele creates a negative cis-element for gene transcription.Our data provide the first evidence that PDCD1 polymorphisms is a genetic factor in pathogenesis of chronic viral infection and reveal the functional significance of the P7209 SNP of the PDCD1.