Association between hepatitis B viral burden in chronic infection and a functional single nucleotide polymorphism of the PDCD1 gene.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
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.
Zheng
Linghua
L
Key Laboratory of Infection and Immunity, Institute of Biophysics, Beijing 100101, China.
Li
Dongling
D
Wang
Fusheng
F
Wu
Hao
H
Li
Xiaozhu
X
Fu
Junliang
J
Chen
Xinyue
X
Wang
Lizhong
L
Liu
Yang
Y
Wang
Shengdian
S
D000328:Adult; D015703:Antigens, CD / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006515:Hepatitis B virus / Q000472:pathogenicity / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000235:genetics* / Q000276:immunology; D006801:Humans; D047668:Inteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D061026:Programmed Cell Death 1 Receptor; D019562:Viral Load / Q000235:genetics*; D014774:Virulence / Q000235:genetics
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor