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

Autor: Kim TH; Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea., Lee EJ; Department of Physiology, Ajou University School of Medicine, Suwon, Korea., Choi JH; Department of Physiology, Ajou University School of Medicine, Suwon, Korea.; Department of Biomedical Science, Graduate School, Ajou University, Suwon, Korea., Yim SY; Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea., Lee S; Department of Computer Science and Engineering, Korea University College of Informatics, Seoul, Korea., Kang J; Department of Computer Science and Engineering, Korea University College of Informatics, Seoul, Korea., Lee YR; Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea., Lee HA; Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea., Choi HS; Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea., Kim ES; Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea., Keum B; Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea., Seo YS; Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea., Yim HJ; Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea., Jeen YT; Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea., Chun HJ; Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea., Lee HS; Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea., Kim CD; Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea., Woo HG; Department of Physiology, Ajou University School of Medicine, Suwon, Korea.; Department of Biomedical Science, Graduate School, Ajou University, Suwon, Korea., Um SH; Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2018 Jul 05; Vol. 13 (7), pp. e0199094. Date of Electronic Publication: 2018 Jul 05 (Print Publication: 2018).
DOI: 10.1371/journal.pone.0199094
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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