PMID- 30985007 OWN - NLM STAT- MEDLINE DCOM- 20200622 LR - 20221207 IS - 1527-3350 (Electronic) IS - 0270-9139 (Linking) VI - 70 IP - 1 DP - 2019 Jul TI - HLA-B*35:01 Allele Is a Potential Biomarker for Predicting Polygonum multiflorum-Induced Liver Injury in Humans. PG - 346-357 LID - 10.1002/hep.30660 [doi] AB - 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 x 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 x 10(-6) ; and PM-DILI versus population controls, OR, 143.9; 95% CI, 30.1-687.5, P = 4.8 x 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. CI - (c) 2019 by the American Association for the Study of Liver Diseases. FAU - Li, Chaopeng AU - Li C AUID- ORCID: 0000-0003-4316-9140 AD - Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China. AD - Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, China. AD - Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, China. AD - National Clinical Research Center for Geriatric Disorders, Changsha, Hunan, China. AD - Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha, Hunan, China. AD - The First Affiliated Hospital of the Medical College, Shihezi University, Shihezi, Xinjiang, China. FAU - Rao, Tai AU - Rao T AD - Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China. AD - Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, China. AD - Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, China. AD - National Clinical Research Center for Geriatric Disorders, Changsha, Hunan, China. FAU - Chen, Xiaoping AU - Chen X AD - Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China. AD - Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, China. AD - Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, China. AD - National Clinical Research Center for Geriatric Disorders, Changsha, Hunan, China. FAU - Zou, Zhengsheng AU - Zou Z AD - The Fifth Medical Center, General Hospital of PLA, Beijing, China. FAU - Wei, Aiwu AU - Wei A AD - The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, China. FAU - Tang, Jinfa AU - Tang J AD - The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, China. FAU - Xiong, Peng AU - Xiong P AD - The Fifth Medical Center, General Hospital of PLA, Beijing, China. FAU - Li, Pengyan AU - Li P AD - The Fifth Medical Center, General Hospital of PLA, Beijing, China. FAU - Jing, Jing AU - Jing J AD - The Fifth Medical Center, General Hospital of PLA, Beijing, China. FAU - He, Tingting AU - He T AD - The Fifth Medical Center, General Hospital of PLA, Beijing, China. FAU - Bai, Zhaofang AU - Bai Z AD - The Fifth Medical Center, General Hospital of PLA, Beijing, China. FAU - Yin, Jiye AU - Yin J AD - Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China. AD - Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, China. AD - Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, China. AD - National Clinical Research Center for Geriatric Disorders, Changsha, Hunan, China. FAU - Tan, Zhirong AU - Tan Z AD - Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China. AD - Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, China. AD - Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, China. AD - National Clinical Research Center for Geriatric Disorders, Changsha, Hunan, China. FAU - Yu, Peng AU - Yu P AD - Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha, Hunan, China. AD - School of Pharmaceutical Science, Central South University, Changsha, Hunan, China. FAU - Zhou, Honghao AU - Zhou H AD - Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China. AD - Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, China. AD - Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, China. AD - National Clinical Research Center for Geriatric Disorders, Changsha, Hunan, China. FAU - Wang, Jiabo AU - Wang J AD - The Fifth Medical Center, General Hospital of PLA, Beijing, China. FAU - Xiao, Xiaohe AU - Xiao X AD - The Fifth Medical Center, General Hospital of PLA, Beijing, China. FAU - Ouyang, Dongsheng AU - Ouyang D AD - Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China. AD - Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, China. AD - Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, China. AD - National Clinical Research Center for Geriatric Disorders, Changsha, Hunan, China. AD - Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha, Hunan, China. LA - eng GR - 201507004-4-3/The Special Research for Traditional Chinese Medicine Industry/International GR - 2016YFC0905001/The National Key Research and Development Program/International GR - 2015ZX09501-004-001-008/The National Development of Key Novel Drugs for Special Projects of China/International GR - 2017ZX09304014/The National Development of Key Novel Drugs for Special Projects of China/International GR - 2017TP1037/The Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples/International GR - 81803837/National Natural Science Foundation of China/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190521 PL - United States TA - Hepatology JT - Hepatology (Baltimore, Md.) JID - 8302946 RN - 0 (Biomarkers) RN - 0 (Drugs, Chinese Herbal) RN - 0 (HLA-B*35:01 antigen) RN - 0 (HLA-B35 Antigen) SB - IM CIN - Hepatology. 2019 Jul;70(1):8-10. PMID: 31155733 MH - Adult MH - Asian People/genetics MH - Biomarkers MH - Chemical and Drug Induced Liver Injury/*genetics MH - Drugs, Chinese Herbal/toxicity MH - Fallopia multiflora/*toxicity MH - Female MH - HLA-B35 Antigen/*genetics MH - Humans MH - Male MH - Middle Aged MH - Pharmacogenomic Variants MH - Pilot Projects MH - Prospective Studies MH - Young Adult EDAT- 2019/04/16 06:00 MHDA- 2020/06/23 06:00 CRDT- 2019/04/16 06:00 PHST- 2018/12/08 00:00 [received] PHST- 2019/03/27 00:00 [accepted] PHST- 2019/04/16 06:00 [pubmed] PHST- 2020/06/23 06:00 [medline] PHST- 2019/04/16 06:00 [entrez] AID - 10.1002/hep.30660 [doi] PST - ppublish SO - Hepatology. 2019 Jul;70(1):346-357. doi: 10.1002/hep.30660. Epub 2019 May 21.