Polymorphisms of type I interferon receptor 1 promoter and their effects on chronic hepatitis B virus infection.
OBJECTIVE
Exposure to HBV leads to a distinct clinical course which is partially pertained to host genetic variability. We aimed to study polymorphisms of type I interferon receptor 1 (IFNAR1) promoter and their potential effects on chronic HBV infection.


METHODS
Polymorphisms of IFNAR1 promoter were identified in 320 chronic hepatitis B patients, 148 spontaneously recovered individuals, 148 healthy Chinese donors and 114 Caucasians. Their functional capability in driving reporter gene expression was analyzed.


RESULTS
Four polymorphic alleles were identified at loci -568, -408, -77 and -3. Association analysis revealed that carriers of alleles -568G, -408C and their related haplotype I were less susceptible to chronic HBV infection whereas those of alleles -568C, -408T and related haplotype III were significantly associated with higher risk to chronic hepatitis B (P<0.01). In a reporter-driven system, the promoter variants with alleles -408C and -3C could drive higher expression of the reporter gene than those with alleles -408T and -3T (P<0.01). Interestingly, an allele with 9 GT repeats at -77 that was rarely found in Chinese but prevalent in Caucasian exhibited the highest transcriptional ability.


CONCLUSIONS
Our results showed that polymorphisms of IFNAR1 promoter may affect, at least in part, the outcomes of HBV infection.
Zhou
Jie
J
Department of Microbiology, The University of Hong Kong, Hong Kong.
Lu
Liwei
L
Yuen
Man-Fung
MF
Lam
Ting-Wa
TW
Chung
Chi-Ping
CP
Lam
Chun-Lit
CL
Zhang
Bin
B
Wang
Song
S
Chen
Yu
Y
Wu
Sharon H W
SH
Poon
Vincent K M
VK
Ng
Fai
F
Chan
Chris C S
CC
Jiang
Shibo
S
Yuen
Kwok-Yung
KY
Zheng
Bo-Jian
BJ
D044466:Asian People / Q000235:genetics; D003289:Convalescence; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D019694:Hepatitis B, Chronic / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D053633:Receptor, Interferon alpha-beta / Q000235:genetics*; D014158:Transcription, Genetic
C507964:IFNAR1 protein, human; D053633:Receptor, Interferon alpha-beta