Published online Mar 28, 2020. doi: 10.3748/wjg.v26.i12.1329
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
Processing time: 114 Days and 2.7 Hours
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.
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.
The objective of this study was to identify SNPs that indicate susceptibility to PM-DILI.
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.
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.
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.
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.