HLA-B*35:01 Allele Is a Potential Biomarker for Predicting Polygonum multiflorum-Induced Liver Injury in Humans.

Abstract

Polygonum multiflorum (PM) is a well-known Chinese herbal medicine that has been reported to induce inflammation-associated idiosyncratic liver injury. This study aimed to identify the genetic basis of susceptibility to PM-drug-induced liver injury (PM-DILI) and to develop biological markers for predicting the risk of PM-DILI in humans. The major histocompatibility complex (MHC) regions of 11 patients with PM-DILI were sequenced, and all human leukocyte antigen (HLA)-type frequencies were compared to the Han-MHC database. An independent replication study that included 15 patients with PM-DILI, 33 patients with other DILI, and 99 population controls was performed to validate the candidate allele by HLA-B PCR sequence-based typing. A prospective cohort study that included 72 outpatients receiving PM for 4 weeks was designed to determine the influence of the risk allele on PM-DILI. In the pilot study, the frequency of HLA-B*35:01 was 45.4% in PM-DILI patients compared with 2.7% in the Han Chinese population (odds ratio [OR], 30.4; 95% confidence interval [CI], 11.7-77.8; P = 1.9 × 10-10 ). In the independent replication study and combined analyses, a logistic regression model confirmed that HLA-B*35:01 is a high-risk allele of PM-DILI (PM-DILI versus other DILI, OR, 86.5; 95% CI, 14.2-527.8, P = 1.0 × 10-6 ; and PM-DILI versus population controls, OR, 143.9; 95% CI, 30.1-687.5, P = 4.8 × 10-10 ). In the prospective cohort study, an asymptomatic increase in transaminase levels was diagnosed in 6 patients, representing a significantly higher incidence (relative risk, 8.0; 95% CI, 1.9-33.2; P < 0.02) in the HLA-B*35:01 carriers (37.5%) than in the noncarriers (4.7%). Conclusion: The HLA-B*35:01 allele is a genetic risk factor for PM-DILI and a potential biomarker for predicting PM-DILI in humans.

• Authors: Chaopeng Li, Tai Rao, Xiaoping Chen, Zhengsheng Zou, Aiwu Wei, Jinfa Tang, Peng Xiong, Pengyan Li, Jing Jing, Tingting He, Zhaofang Bai, Jiye Yin, Zhirong Tan, Peng Yu, Honghao Zhou, Jiabo Wang, Xiaohe Xiao, Dongsheng Ouyang
• Journal: Hepatology (Baltimore, Md.) (Hepatology) Vol. 70 Issue 1 Pg. 346-357 (07 2019) ISSN: 1527-3350 [Electronic] United States
• PMID: 30985007 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 by the American Association for the Study of Liver Diseases.

Chemical References

• Biomarkers
• Drugs, Chinese Herbal
• HLA-B*35:01 antigen
• HLA-B35 Antigen

Topics

• Adult
• Asian People (genetics)
• Biomarkers
• Chemical and Drug Induced Liver Injury (genetics)
• Drugs, Chinese Herbal (toxicity)
• Fallopia multiflora (toxicity)
• Female
• HLA-B35 Antigen (genetics)
• Humans
• Male
• Middle Aged
• Pharmacogenomic Variants
• Pilot Projects
• Prospective Studies
• Young Adult