期刊
HUMAN MUTATION
卷 32, 期 10, 页码 1128-1136出版社
WILEY-BLACKWELL
DOI: 10.1002/humu.21544
关键词
ESR1; genetic susceptibility; haplotype; hepatitis B; liver cirrhosis
资金
- Chinese NCET [2007-0146]
- National Natural Science Foundation of China [30671850]
- National Basic Research Program of China, 973 Program [2007CB512903]
- State Key Project Specialized for Infectious Diseases [2008ZX10002-007]
The hepatic fibrogenesis and sexual dimorphism of hepatitis B virus-related liver cirrhosis (HBV-LC) are related to estrogen and its receptors. Abnormal expression of estrogen receptor a (ESR1) is implicated in the development of cirrhosis in both animal models and humans. Here, we examine whether the ESR1 polymorphisms are related to HBV-LC risk among chronic HBV carriers, and we investigate the functional significance of positively associated polymorphisms. A total of 2,404 unrelated Chinese HBV carriers were recruited to conduct the two-stage designed case-control study. Two ESR1 haplotype tagging polymorphisms, c.30T>C (rs2077647) and c.453-397T>C (rs2234693), were genotyped in 1,285 patients with HBV-LC and in 1,119 asymptomatic HBV carriers. We observed a significantly increased susceptibility to HBV-LC associated with the c.30C allele (P = 4.2x10(-8)), c.453-397C allele (P = 2.0x10(-8)), and [c.30C; c.453-397C] haplotype (Dominant model, P = 8.85x10(-10), odds ratio = 1.50, 95% CI 1.32 similar to 1.71) compared with the T alleles and (c.30T; c.453-397T) haplotype of c.30T>C and c.453-397T>C polymorphisms, respectively. Functional analyses were conducted to verify the biological functions of the associated genetic variations and showed that the c.453-397T>C polymorphism is a novel c.453-397C allele-specific and c-myb-dependent enhancer-like cis-acting regulatory variation and could be part of the genetic variations underlying the susceptibility of individuals to HBV-LC. Hum Mutat 32:1128-1136, 2011. (C) 2011 Wiley-Liss, Inc.
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