Estrogen receptor alpha gene polymorphisms and risk of HBV-related acute liver failure in the Chinese population.
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.
Institute of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, P.R. China.
Zehui
Z
Yan
Wenting
W
Tan
Yunjie
Y
Dan
Wenli
W
Zhao
Chunqing
C
Deng
Yuming
Y
Wang
Guohong
G
Deng
D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D002681:China; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006509:Hepatitis B / Q000150:complications*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D017114:Liver Failure, Acute / Q000208:ethnology* / Q000235:genetics* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011946:Receptors, Antigen / Q000737:chemistry
D047628:Estrogen Receptor alpha; D011946:Receptors, Antigen; C030500:hepatitis B surface antigen receptor