鉴定与慢性乙型肝炎乙型肝炎表面抗原血清清除相关的新型

StephenW

PLoS One. 2018 Jul 5;13(7):e0199094. doi: 10.1371/journal.pone.0199094. eCollection 2018.
Identification of novel susceptibility loci associated with hepatitis B surface antigen seroclearance in chronic hepatitis B.
Kim TH1, Lee EJ2, Choi JH2,3, Yim SY1, Lee S4, Kang J4, Lee YR1, Lee HA1, Choi HS1, Kim ES1, Keum B1, Seo YS1, Yim HJ1, Jeen YT1, Chun HJ1, Lee HS1, Kim CD1, Woo HG2,3, Um SH1.
Author information

1
    Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
2
    Department of Physiology, Ajou University School of Medicine, Suwon, Korea.
3
    Department of Biomedical Science, Graduate School, Ajou University, Suwon, Korea.
4
    Department of Computer Science and Engineering, Korea University College of Informatics, Seoul, Korea.

Abstract
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.

PMID:
    29975729
DOI:
    10.1371/journal.pone.0199094

StephenW

PLoS One。 2018年7月5日; 13（7）：e0199094。 doi：10.1371 / journal.pone.0199094。 eCollection 2018。
鉴定与慢性乙型肝炎乙型肝炎表面抗原血清清除相关的新型易感位点。
Kim TH1，Lee EJ2，Choi JH2,3，Yim SY1，Lee S4，Kang J4，Lee YR1，Lee HA1，Choi HS1，Kim ES1，Keum B1，Seo YS1，Yim HJ1，Jeen YT1，Chun HJ1，Lee HS1， Kim CD1，Woo HG2,3，Um SH1。
作者信息

1
    韩国首尔大学医学院内科。
2
    韩国水原市Ajou大学医学院生理学系。
3
    韩国水原市Ajou大学研究生院生物医学科
4
    韩国首尔大学信息学院计算机科学与工程系。

抽象
背景/目的：

乙型肝炎病毒（HBV）表面抗原（HBsAg）的血清清除被认为是慢性乙型肝炎（CHB）的功能性治疗，尽管很少发生。最近，几项全基因组关联研究（GWAS）揭示了与HBV感染临床过程相关的各种遗传改变。然而，所有这些研究都集中在HBV感染进展为慢性，并且由于HBV基因型的异质性而应用受到限制。在本研究中，我们旨在确定具有同源病毒基因型的CHB患者中HBsAg血清清除的易感性遗传标记。
方法：

100名CHB患者在60岁之前经历过HBsAg血清清除，另有100名CHB患者即使在60岁之后也显示出高血清HBsAg水平。使用参与者的血液样品进行极端表型GWAS。
结果：

我们在11q12.1，rs171941（P = 3.52×10-）确定了三个单核苷酸多态性rs7944135（P = 4.17×10-6，比值比[OR] = 4.16,95％可信区间[CI] = 2.27-7.63）。 6，OR = 3.69,95％CI = 2.13-6.42）在5q14.1和rs6462008（P = 3.40×10-6，OR = 0.34,95％CI = 0.22-0.54）在7p15.2作为新的易感位点与CHB患者的HBsAg血清清除率相关。这些基因座的侧翼基因包括MPEG1，DTX4，MTX3和HOXA13被认为具有功能意义。此外，通过功能分析，CXCL13也被认为是相关的。
结论：

据我们所知，这项研究是关于CHB患者HBsAg血清清除的第一个GWAS。我们确定了治疗CHB的新易感位点，为其病理生理学提供了新的见解。

结论：
    29975729
DOI：
    10.1371 / journal.pone.0199094