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Identification of novel susceptibility loci associated with hepatitis B surface antigen seroclearance in chronic hepatitis B

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dc.contributor.authorKim, Tae Hyung-
dc.contributor.authorLee, Eun-Ju-
dc.contributor.authorChoi, Ji-Hye-
dc.contributor.authorYim, Sun Young-
dc.contributor.authorLee, Sunwon-
dc.contributor.authorKang, Jaewoo-
dc.contributor.authorLee, Yoo Ra-
dc.contributor.authorLee, Han Ah-
dc.contributor.authorChoi, Hyuk Soon-
dc.contributor.authorKim, Eun Sun-
dc.contributor.authorKeum, Bora-
dc.contributor.authorSeo, Yeon Seok-
dc.contributor.authorYim, Hyung Joon-
dc.contributor.authorJeen, Yoon Tee-
dc.contributor.authorChun, Hoon Jai-
dc.contributor.authorLee, Hong Sik-
dc.contributor.authorKim, Chang Duck-
dc.contributor.authorWoo, Hyun Goo-
dc.contributor.authorUm, Soon Ho-
dc.description.abstractBackground/Aims The seroclearance of hepatitis B virus (HBV) surface antigen (HBsAg) is regarded as a functional cure of chronic hepatitis B (CHB) although it occurs rarely. Recently, several genome-wide association studies (GWASs) revealed various genetic alterations related to the clinical course of HBV infection. However, all of these studies focused on the progression of HBV infection to chronicity and had limited application because of the heterogeneity of HBV genotypes. In the present study, we aimed to determine susceptibility genetic markers for seroclearance of HBsAg in CHB patients with a homogenous viral genotype. Methods One hundred patients with CHB who had experienced HBsAg seroclearance before 60 years of age and another 100 with CHB showing high serum levels of HBsAg even after 60 years of age were enrolled. Extreme-phenotype GWAS was conducted using blood samples of participants. Results We identified three single nucleotide polymorphisms, rs7944135 (P = 4.17 × 10−6, odds ratio [OR] = 4.16, 95% confidence interval [CI] = 2.27–7.63) at 11q12.1, rs171941 (P = 3.52×10−6, OR = 3.69, 95% CI = 2.13–6.42) at 5q14.1, and rs6462008 (P = 3.40×10−6, OR = 0.34, 95% CI = 0.22–0.54) at 7p15.2 as novel susceptibility loci associated with HBsAg seroclearance in patients with CHB. The flanking genes at these loci including MPEG1, DTX4, MTX3, and HOXA13 were suggested to have functional significance. In addition, through functional analysis, CXCL13 was also presumed to be related. Conclusions To the best of our knowledge, this study is the first GWAS regarding the seroclearance of HBsAg in CHB patients. We identify new susceptibility loci for cure of CHB, providing new insights into its pathophysiology.-
dc.publisherPublic Library of Science-
dc.titleIdentification of novel susceptibility loci associated with hepatitis B surface antigen seroclearance in chronic hepatitis B-
dc.contributor.affiliatedAuthorKim, Tae Hyung-
dc.contributor.affiliatedAuthorYim, Sun Young-
dc.contributor.affiliatedAuthorLee, Han Ah-
dc.contributor.affiliatedAuthorChoi, Hyuk Soon-
dc.contributor.affiliatedAuthorKim, Eun Sun-
dc.contributor.affiliatedAuthorKeum, Bora-
dc.contributor.affiliatedAuthorSeo, Yeon Seok-
dc.contributor.affiliatedAuthorYim, Hyung Joon-
dc.contributor.affiliatedAuthorJeen, Yoon Tee-
dc.contributor.affiliatedAuthorChun, Hoon Jai-
dc.contributor.affiliatedAuthorLee, Hong Sik-
dc.contributor.affiliatedAuthorKim, Chang Duck-
dc.contributor.affiliatedAuthorUm, Soon Ho-
dc.identifier.bibliographicCitationPLoS ONE, v.13, no.7-
dc.relation.isPartOfPLoS ONE-
dc.citation.titlePLoS ONE-
dc.relation.journalResearchAreaScience & Technology - Other Topics-
dc.relation.journalWebOfScienceCategoryMultidisciplinary Sciences-
dc.subject.keywordPlusVIRUS X PROTEIN-
dc.subject.keywordPlusGENOME-WIDE ASSOCIATION-
dc.subject.keywordPlus7 AGONIST GS-9620-
dc.subject.keywordPlusHBSAG SEROCLEARANCE-
dc.subject.keywordPlusDISEASE PROGRESSION-
dc.subject.keywordPlusDELAYED CLEARANCE-
dc.subject.keywordPlusCHRONIC CARRIERS-
dc.subject.keywordPlusSERUM HBSAG-
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5. Others > Others(Medicine) > 1. Journal Articles
2. Clinical Science > Department of Gastroenterology and Hepatology > 1. Journal Articles


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Lee, Hong Sik
안암병원 (Department of Gastroenterology and Hepatology, Anam Hospital)
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