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...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC6033413?pdf=render |
| _version_ | 1828808280830377984 |
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| author | Tae Hyung Kim Eun-Ju Lee Ji-Hye Choi Sun Young Yim Sunwon Lee Jaewoo Kang Yoo Ra Lee Han Ah Lee Hyuk Soon Choi Eun Sun Kim Bora Keum Yeon Seok Seo Hyung Joon Yim Yoon Tae Jeen Hoon Jai Chun Hong Sik Lee Chang Duck Kim Hyun Goo Woo Soon Ho Um |
| author_facet | Tae Hyung Kim Eun-Ju Lee Ji-Hye Choi Sun Young Yim Sunwon Lee Jaewoo Kang Yoo Ra Lee Han Ah Lee Hyuk Soon Choi Eun Sun Kim Bora Keum Yeon Seok Seo Hyung Joon Yim Yoon Tae Jeen Hoon Jai Chun Hong Sik Lee Chang Duck Kim Hyun Goo Woo Soon Ho Um |
| author_sort | Tae Hyung Kim |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-12T08:38:25Z |
| format | Article |
| id | doaj.art-259fd6336d224d208399bababade2cdd |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T08:38:25Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-259fd6336d224d208399bababade2cdd2022-12-22T00:30:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01137e019909410.1371/journal.pone.0199094Identification of novel susceptibility loci associated with hepatitis B surface antigen seroclearance in chronic hepatitis B.Tae Hyung KimEun-Ju LeeJi-Hye ChoiSun Young YimSunwon LeeJaewoo KangYoo Ra LeeHan Ah LeeHyuk Soon ChoiEun Sun KimBora KeumYeon Seok SeoHyung Joon YimYoon Tae JeenHoon Jai ChunHong Sik LeeChang Duck KimHyun Goo WooSoon Ho UmBACKGROUND/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.http://europepmc.org/articles/PMC6033413?pdf=render |
| spellingShingle | Tae Hyung Kim Eun-Ju Lee Ji-Hye Choi Sun Young Yim Sunwon Lee Jaewoo Kang Yoo Ra Lee Han Ah Lee Hyuk Soon Choi Eun Sun Kim Bora Keum Yeon Seok Seo Hyung Joon Yim Yoon Tae Jeen Hoon Jai Chun Hong Sik Lee Chang Duck Kim Hyun Goo Woo Soon Ho Um Identification of novel susceptibility loci associated with hepatitis B surface antigen seroclearance in chronic hepatitis B. PLoS ONE |
| 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 |
| url | http://europepmc.org/articles/PMC6033413?pdf=render |
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