Polymorphisms of type I interferon receptor 1 promoter and their effects on chronic hepatitis B virus infection

Autor: Bin Zhang, Sharon H.W. Wu, F Ng, Kwok-Yung Yuen, Jie Zhou, Shibo Jiang, Bo-Jian Zheng, Man-Fung Yuen, Vincent Kwok-Man Poon, Yu Chen, Chun-Lit Lam, Ting-Wa Lam, Song Wang, Chris Chung-Sing Chan, Liwei Lu, Chi-Ping Chung
Rok vydání: 2007
Předmět:
Zdroj: Journal of Hepatology. 46:198-205
ISSN: 0168-8278
DOI: 10.1016/j.jhep.2006.08.017
Popis: 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.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.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 (P0.01). 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 (P0.01). Interestingly, an allele with 9 GT repeats at -77 that was rarely found in Chinese but prevalent in Caucasian exhibited the highest transcriptional ability.Our results showed that polymorphisms of IFNAR1 promoter may affect, at least in part, the outcomes of HBV infection.
Databáze: OpenAIRE