title: Association of estrogen receptor alpha polymorphisms with susceptibility to chronic hepatitis B virus infection.
abstract: Several studies have demonstrated that estrogen receptor alpha (ESR1) participates in the pathogenesis of persistent hepatitis B virus (HBV) infection. To examine whether polymorphisms at the ESR1 gene locus are associated with persistent HBV infection, we resequenced ESR1 genomic region for single nucleotide polymorphisms (SNPs) in 27 unrelated Chinese. Two haplotype-tagged SNPs (htSNP), T29C and A252966G, were selected for genotyping in 1,277 persistent HBV-infected cases, 748 spontaneously recovered controls, and 293 nuclear families using polymerase chain reaction (PCR)-restriction fragment length polymorphism (PCR-RFLP) analysis. We observed that the subjects bearing ESR1 29T/T genotype had an increased susceptibility to persistent HBV infection compared to those bearing at least one 29C allele (odds ratio 1.41; 95% CI, 1.17-1.71, P < .001). Consistent with the results of population-based association study, a significantly greater than expected transmission of the 29T allele (56.4%) from heterozygous parents to offspring with persistent HBV infection was observed (chi2 = 4.60, P = .033) using the transmission-disequilibrium test (TDT) in 293 nuclear families. Linkage disequilibrium (LD) mapping analysis indicated that the T29C polymorphism contained within a LD block located from promoter region to intron 3 of ESR1, suggesting that the strong association detected with T29C in ESR1 originated from ESR1 itself. In conclusion, our results suggest that the genetic variation at the ESR1 locus influences susceptibility to persistent HBV infection in a Chinese population.
authors.affiliation: Department of Infectious Diseases, Southwest Hospital, Chongqing, China.
authors.forename: Guohong
authors.initials: G
authors.lastname: Deng
authors.forename: Gangqiao
authors.initials: G
authors.lastname: Zhou
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhai
authors.forename: Shuqing
authors.initials: S
authors.lastname: Li
authors.forename: Xuhong
authors.initials: X
authors.lastname: Li
authors.forename: Ya
authors.initials: Y
authors.lastname: Li
authors.forename: Ruifang
authors.initials: R
authors.lastname: Zhang
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Yao
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
authors.forename: Boqing
authors.initials: B
authors.lastname: Qiang
authors.forename: Yuming
authors.initials: Y
authors.lastname: Wang
authors.forename: Fuchu
authors.initials: F
authors.lastname: He
mesh_terms: D000328:Adult; D000409:Alanine; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D002874:Chromosome Mapping; D003545:Cysteine; D047628:Estrogen Receptor alpha; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D019694:Hepatitis B, Chronic / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011960:Receptors, Estrogen / Q000235:genetics*; D013912:Threonine
chemical_list: D047628:Estrogen Receptor alpha; D011960:Receptors, Estrogen; D013912:Threonine; D003545:Cysteine; D000409:Alanine