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Estrogen receptor alpha gene polymorphisms and risk of HBV-related acute liver failure in the Chinese population.

ABSTRACT: BACKGROUND: The sexual dimorphism of hepatitis B virus (HBV) -related liver diseases is related with estrogen and its receptors. Recent reports indicate that abnormal expression of estrogen receptor alpha (ESR1) may be a hallmark for the progression of liver disease and HBV carriers presenting variant ESR1 have an extremely aggressive clinical course. Here we examine whether the ESR1 polymorphisms or its haplotypes are related to HBV-related acute liver failure (ALF) risk among chronic HBV carriers in a Chinese population. METHODS: A total of 1216 unrelated Han Chinese HBV carriers were recruited in this hospital-based case-control study, including 359 HBV surface antigen (HBsAg) carriers affected with ALF and 857 asymptomatic HBsAg carriers. Two ESR1 haplotype tagging polymorphisms, c.30?T?>?C (rs2077647) and c.453-397?T?>?C (rs2234693), were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. RESULTS: We observed a significantly increased susceptibility to HBV-ALF associated with the c.30?C allele (P?=?8.65?×?10-4), c.453-397?C allele (5.37?×?10-4) and [c.30?C; c.453-397?C] haplotype (Dominant model, P =0.0004, odds ratio?=?1.53, 95% CI 1.23?~?1.96) compared with the T alleles and [c.30?T; c.453-397?T] haplotype of c.30?T?>?C and c.453-397?T?>?C polymorphisms, respectively. CONCLUSIONS: Our study suggests that [c.30?C; c.453-397?C] haplotype may be a risk factor for genetic susceptibility to HBV-related ALF in the Chinese population. It also emphasizes the importance of ESR1 in the pathophysiology of HBV-related ALF on the population level.

SUBMITTER: Yan Z

PROVIDER: S-EPMC3412699 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Estrogen receptor alpha gene polymorphisms and risk of HBV-related acute liver failure in the Chinese population.

Yan Zehui Z Tan Wenting W Dan Yunjie Y Zhao Wenli W Deng Chunqing C Wang Yuming Y Deng Guohong G

BMC medical genetics 20120624

<h4>Background</h4>The sexual dimorphism of hepatitis B virus (HBV) -related liver diseases is related with estrogen and its receptors. Recent reports indicate that abnormal expression of estrogen receptor alpha (ESR1) may be a hallmark for the progression of liver disease and HBV carriers presenting variant ESR1 have an extremely aggressive clinical course. Here we examine whether the ESR1 polymorphisms or its haplotypes are related to HBV-related acute liver failure (ALF) risk among chronic HB ...[more]

PMID: 22727021

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Project description:BACKGROUNDHBV-related acute-on-chronic liver failure (HBV-ACLF) is hallmarked by high short-term mortality rates, calling for accurate prognostic biomarkers for initial risk stratification.METHODSThree tandem mass tag-labeled (TMT-labeled) quantitative proteomic studies were performed on 10 patients with HBV-related acute hepatic decompensation and on 20 patients with HBV-ACLF. Candidate biomarkers were preliminarily verified in a cross-sectional cohort (n = 144) and further confirmed in 2 prospective cohorts (n = 207 and n = 148).RESULTSPlasminogen, a potential prognostic biomarker for HBV-ACLF, was identified by TMT quantitative proteomics and preliminarily verified in the cross-sectional cohort. Further validation with a prospective cohort (n = 207) showed that plasminogen levels at admission were significantly lower (P < 0.001) in HBV-ACLF nonsurvivors than in survivors. The cumulative survival duration of patients with high plasminogen levels was significantly longer (P < 0.001) than that of patients with low plasminogen levels. During hospitalization, plasminogen levels significantly decreased (P = 0.008) in the deterioration group but significantly increased (P < 0.001) in the improvement group. Additionally, plasminogen levels gradually increased in survivors but gradually decreased in nonsurvivors. The P5 score, a prognostic panel incorporating plasminogen levels, hepatic encephalopathy occurrence, age, international normalized ratio (INR), and total bilirubin, was significantly superior to the Child-Pugh, Model for End-stage Liver Disease (MELD), Chronic Liver Failure Consortium ACLF (CLIF-C ACLF), Chinese Group on the Study of Severe Hepatitis B (COSSH), and HINT (a prognostic score based on hepatic encephalopathy occurrence, INR, neutrophil count, and thyroid-stimulating hormone) scores (all P < 0.05). The performances of the plasminogen level and P5 score were validated in a second multicenter, prospective cohort (n = 148).CONCLUSIONSPlasminogen is a promising prognostic biomarker for HBV-ACLF, and sequential plasminogen measurements could profile the clinical course of HBV-ACLF. P5 is a high-performance prognostic score for HBV-ACLF.FUNDINGThe National Key Research and Development Program (2017YFC1200204); the National Natural Science Foundation of China (81400589, 81600497); the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (81121002); the Chinese High-Tech Research and Development Programs (2012AA020204); the National S&T Major Project (2012ZX10002004); and the Zhejiang Provincial Medicine and Health Science and Technology Project (2016147735).

Dataset Information

Estrogen receptor alpha gene polymorphisms and risk of HBV-related acute liver failure in the Chinese population.

Publications

Estrogen receptor alpha gene polymorphisms and risk of HBV-related acute liver failure in the Chinese population.

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