A regulatory polymorphism in interferon-gamma receptor 1 promoter is associated with the susceptibility to chronic hepatitis B virus infection.
The antiviral cascade triggered by interferon-gamma (IFN-gamma) represents a vital event for eradicating hepatitis B virus (HBV) in experimental animals. IFN-gamma signaling is mediated through the ligand binding to IFN-gamma receptor 1 (IFNGR1). Control of IFNGR1 expression level is one of the mechanisms by which cells modulate the potency of IFN-gamma signaling. In this study, we comprehensively investigated the single nucleotide polymorphisms (SNPs) in IFNGR1 gene and correlated their occurrence to susceptibility to HBV infection in a Chinese population. A total of 983 participants, including 361 chronic hepatitis B patients, 256 individuals who had spontaneously recovered from HBV infection, and 366 healthy control subjects, were enrolled in the study. Polymerase chain reaction-restriction fragment length polymorphism was used to identify seven SNPs (-611A/G, -56C/T, 40G/A, 95C/T, 130A/G, 20685A/G, 21227T/C) in IFNGR1 gene. We found that -56C and -56T allele were associated with viral clearance and viral persistence, respectively (P = 0.014). In a reporter-driven assay, we validated that the promoter variant with -56C exhibited a higher transcription level than that with -56T in HepG2 cells in a cell-type-specific pattern. We conclude that a functional -56C/T SNP in IFNGR1 promoter is associated with the clinical outcome of HBV infection in this Chinese population.
Zhou
Jie
J
Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong, Hong Kong SAR, China.
Chen
Ding-Qiang
DQ
Poon
Vincent K M
VK
Zeng
Yong
Y
Ng
Fai
F
Lu
Liwei
L
Huang
Jian-Dong
JD
Yuen
Kwok-Yung
KY
Zheng
Bo-Jian
BJ
D002460:Cell Line; D045744:Cell Line, Tumor; D016009:Chi-Square Distribution; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006367:HeLa Cells; D019694:Hepatitis B, Chronic / Q000235:genetics* / Q000821:virology; D006801:Humans; D016015:Logistic Models; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008163:Luminescent Measurements; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D017471:Receptors, Interferon / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014162:Transfection; D000096743:Interferon gamma Receptor
D008156:Luciferases; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor