TY - JOUR
T1 - Polymorphisms of type I interferon receptor 1 promoter and their effects on chronic hepatitis B virus infection
AU - Zhou, Jie
AU - Lu, Liwei
AU - Yuen, Man Fung
AU - Lam, Ting Wa
AU - Chung, Chi Ping
AU - Lam, Chun Lit
AU - Zhang, Bin
AU - Wang, Song
AU - Chen, Yu
AU - Wu, Sharon HW
AU - Poon, Vincent KM
AU - Ng, Fai
AU - Chan, Chris CS
AU - Jiang, Shibo
AU - Yuen, Kwok Yung
AU - Zheng, Bo Jian
PY - 2007/2
Y1 - 2007/2
N2 - Background/Aims: 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.
AB - Background/Aims: 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.
KW - Chronic HBV infection
KW - Haplotypes
KW - IFNAR1 promoter polymorphisms
KW - Transcriptional activity
UR - http://www.scopus.com/inward/record.url?scp=33845678522&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33845678522&partnerID=8YFLogxK
U2 - 10.1016/j.jhep.2006.08.017
DO - 10.1016/j.jhep.2006.08.017
M3 - Article
C2 - 17125879
AN - SCOPUS:33845678522
SN - 0168-8278
VL - 46
SP - 198
EP - 205
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 2
ER -