Copyright
©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
Single-nucleotide polymorphisms of HLA and Polygonum multiflorum-induced liver injury in the Han Chinese population
Wan-Na Yang, Li-Li Pang, Ji-Yuan Zhou, Yuan-Wang Qiu, Liang Miao, Shou-Yun Wang, Xiang-Zhong Liu, Kang-An Tan, Wan-Wan Shi, Gui-Qiang Wang, Feng-Qin Hou
Wan-Na Yang, Kang-An Tan, Wan-Wan Shi, Gui-Qiang Wang, Feng-Qin Hou, Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, China
Li-Li Pang, Department of Gastroenterology and Hematology, AEROSPACE 731 Hospital, Beijing 100074, China
Ji-Yuan Zhou, Department of Gastroenterology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, Guangdong Province, China
Yuan-Wang Qiu, Department of Liver Diseases, the Wuxi Fifth Affiliated Hospital of Jiangnan University, Wuxi 214011, Jiangsu Province, China
Liang Miao, Shou-Yun Wang, Department of Liver Diseases, the Third Hospital of Qinhuangdao, Qinhuangdao 066001, Hebei Province, China
Xiang-Zhong Liu, Department of Liver Diseases, Yantai City Hospital for Infectious Diseases, Yantai 264001, Shandong Province, China
Gui-Qiang Wang, Feng-Qin Hou, Department of Infectious Diseases, Peking University International Hospital, Beijing 102206, China
Gui-Qiang Wang, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, Zhejiang Province, China
Author contributions: Yang WN contributed to data collection, analyses, writing and revision; Pang LL, Zhou JY, Qiu YW, Miao L, Wang SY, Liu XZ, Tan KA and Shi WW contributed to data collection; Hou FQ and Wang GQ contributed to study design and critical revision of the manuscript for important intellectual content; Hou FQ had primary responsibility and all authors approved the final paper.
Supported by the National Natural Science Foundation of China, No. 81470849; and the China Mega-Project for Infectious Diseases, No. 2017ZX10203202.
Institutional review board statement: The study was approved by the Human Research Committee of Peking University First Hospital.
Informed consent statement: All patients gave informed consent.
Conflict-of-interest statement: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Feng-Qin Hou, MD, Associate Professor, Chief Physician, Professor of Medicine, Department of Infectious Diseases, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing 100034, China. houfqys@139.com
Received: December 5, 2019
Peer-review started: December 5, 2019
First decision: January 12, 2020
Revised: February 7, 2020
Accepted: February 28, 2020
Article in press: February 28, 2020
Published online: March 28, 2020
ARTICLE HIGHLIGHTS
Research background
Polygonum multiflorum (PM) is a well-known traditional Chinese herbal medicine. However, reports of PM-induced liver injury (PM-DILI) have been increasing in recent years. To increase the safe use of PM, the identification of biomarkers to prevent and diagnose PM-DILI is essential.
Research motivation
Susceptibility to DILI is considered to be genetically determined. Recently, an association between HLA-B*35:01 and PM-DILI was reported. However, HLA genotyping is time consuming and expensive compared with the detection of single-nucleotide polymorphisms (SNPs). The identification of SNPs which could serve as biomarkers of PM-DILI would improve the application of PM and produce considerable economic benefits.
Research objectives
The objective of this study was to identify SNPs that indicate susceptibility to PM-DILI.
Research methods
The study enrolled 73 PM-DILI patients, 118 other drug-induced liver injury (other-DILI) patients and 191 healthy controls. Whole-exome sequencing was performed on 8 PM-DILI patients and 8 healthy controls who were randomly selected from 73 PM-DILI patients and 191 healthy controls. Nineteen SNPs which were selected from previous whole-exome sequencing were screened in the remaining subjects using the MassARRAY system. HLA-B high-resolution genotyping was performed for 73 PM-DILI patients and 118 other-DILI patients. The Han-MHC database was selected as a population control for HLA-B analysis. SPSS (version 20.0, SPSS Inc., Chicago, IL, United States), PLINK software (version 1.07), MedCalc for Windows (version 15.2, MedCalc Software, Ostend, Belgium), and GraphPad QuickCalcs (GraphPad Software Inc., La Jolla, CA, United States) were used for statistical analyses.
Research results
Compared with the control group, three SNPs, rs111686806 in the HLA-B gene, rs1055348 in the HLA-B gene, and rs202047044 in the HLA-DRB1 gene were associated with PM-DILI. Only rs1055348 had a significantly higher frequency in the PM-DILI group than in the other-DILI group (P = 1.84 × 10-10), which suggested that rs1055348 was a specific risk factor for PM-DILI. HLA-B*35:01 was confirmed to be associated with PM-DILI. Furthermore, rs1055348 may serve as a tag for HLA-B*35:01 with 100% sensitivity and > 95% specificity.
Research conclusions
rs111686806, rs1055348 and rs202047044 are associated with PM-DILI, and rs1055348 is specific to PM-DILI. As a tag for HLA-B*35:01, rs1055348 may be used as an alternative predictive biomarker of PM-DILI.
Research perspectives
Screening for tag rs1055348 before consuming PM would improve the safe use of PM and produce considerable economic benefits. A prospective study with a larger sample size of patients taking PM only is needed to further evaluate the role of rs1055348 in the HLA-B gene in PM-DILI.
