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

BACKGROUND/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...

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Autores principales: Kim, Tae Hyung, Lee, Eun-Ju, Choi, Ji-Hye, Yim, Sun Young, Lee, Sunwon, Kang, Jaewoo, Lee, Yoo Ra, Lee, Han Ah, Choi, Hyuk Soon, Kim, Eun Sun, Keum, Bora, Seo, Yeon Seok, Yim, Hyung Joon, Jeen, Yoon Tae, Chun, Hoon Jai, Lee, Hong Sik, Kim, Chang Duck, Woo, Hyun Goo, Um, Soon Ho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6033413/
https://www.ncbi.nlm.nih.gov/pubmed/29975729
http://dx.doi.org/10.1371/journal.pone.0199094
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author Kim, Tae Hyung
Lee, Eun-Ju
Choi, Ji-Hye
Yim, Sun Young
Lee, Sunwon
Kang, Jaewoo
Lee, Yoo Ra
Lee, Han Ah
Choi, Hyuk Soon
Kim, Eun Sun
Keum, Bora
Seo, Yeon Seok
Yim, Hyung Joon
Jeen, Yoon Tae
Chun, Hoon Jai
Lee, Hong Sik
Kim, Chang Duck
Woo, Hyun Goo
Um, Soon Ho
author_facet Kim, Tae Hyung
Lee, Eun-Ju
Choi, Ji-Hye
Yim, Sun Young
Lee, Sunwon
Kang, Jaewoo
Lee, Yoo Ra
Lee, Han Ah
Choi, Hyuk Soon
Kim, Eun Sun
Keum, Bora
Seo, Yeon Seok
Yim, Hyung Joon
Jeen, Yoon Tae
Chun, Hoon Jai
Lee, Hong Sik
Kim, Chang Duck
Woo, Hyun Goo
Um, Soon Ho
author_sort Kim, Tae Hyung
collection PubMed
description BACKGROUND/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.
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spelling pubmed-60334132018-07-19 Identification of novel susceptibility loci associated with hepatitis B surface antigen seroclearance in chronic hepatitis B Kim, Tae Hyung Lee, Eun-Ju Choi, Ji-Hye Yim, Sun Young Lee, Sunwon Kang, Jaewoo Lee, Yoo Ra Lee, Han Ah Choi, Hyuk Soon Kim, Eun Sun Keum, Bora Seo, Yeon Seok Yim, Hyung Joon Jeen, Yoon Tae Chun, Hoon Jai Lee, Hong Sik Kim, Chang Duck Woo, Hyun Goo Um, Soon Ho PLoS One Research Article BACKGROUND/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. Public Library of Science 2018-07-05 /pmc/articles/PMC6033413/ /pubmed/29975729 http://dx.doi.org/10.1371/journal.pone.0199094 Text en © 2018 Kim et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Kim, Tae Hyung
Lee, Eun-Ju
Choi, Ji-Hye
Yim, Sun Young
Lee, Sunwon
Kang, Jaewoo
Lee, Yoo Ra
Lee, Han Ah
Choi, Hyuk Soon
Kim, Eun Sun
Keum, Bora
Seo, Yeon Seok
Yim, Hyung Joon
Jeen, Yoon Tae
Chun, Hoon Jai
Lee, Hong Sik
Kim, Chang Duck
Woo, Hyun Goo
Um, Soon Ho
Identification of novel susceptibility loci associated with hepatitis B surface antigen seroclearance in chronic hepatitis B
title Identification of novel susceptibility loci associated with hepatitis B surface antigen seroclearance in chronic hepatitis B
title_full Identification of novel susceptibility loci associated with hepatitis B surface antigen seroclearance in chronic hepatitis B
title_fullStr Identification of novel susceptibility loci associated with hepatitis B surface antigen seroclearance in chronic hepatitis B
title_full_unstemmed Identification of novel susceptibility loci associated with hepatitis B surface antigen seroclearance in chronic hepatitis B
title_short Identification of novel susceptibility loci associated with hepatitis B surface antigen seroclearance in chronic hepatitis B
title_sort identification of novel susceptibility loci associated with hepatitis b surface antigen seroclearance in chronic hepatitis b
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6033413/
https://www.ncbi.nlm.nih.gov/pubmed/29975729
http://dx.doi.org/10.1371/journal.pone.0199094
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