The liver biopsies obtained from 12 patients with PM‐DILI suggested that acute hepatitis and acute cholestatic hepatitis were two major types of histological patterns. ª Notes - See notes for ambiguous combinations of alleles. Allele Frequency Net Database : About us: Links: Publications: Automated Access: FAQs: Contact : Home : Populations : HLA: KIR : Other polymorphisms : HLA-ADR : KDDB : HLA data sets . HLA-NET defined standards for producing high quality data for HLA genotyping and proposed guidelines for reporting typing ambiguities. HLA-DP is a protein/peptide-antigen receptor and graft-versus-host disease antigen that is composed of 2 subunits, DPα and DPβ. - HLA searching options. Overall, we hypothesized that the HLA genotype might be related to PM‐DILI. Learn more. HLA‐B*35:01 was the most significant independent signal of the other HLA‐B alleles. HLA typing was performed by comparing contigs with currently known HLA gene sequences in the ImMunoGeneTics/HLA database (release 3.30.0). Es sind mehr als 2.400 unterschiedliche HLA-A-Allele bekannt, die mehr als 1.700 verschiedene aktive Proteine kodieren. HLA‐B*35:01 is a common HLA‐B allele in Han Chinese, with a frequency of 2%‐5% according to the Allele Frequencies net database. However, 90.9% (10/11) of PM‐DILI patients carried the allele. HLA class I alleles are usually associated with specific cluster of differentiation 8–positive (CD8+) cytotoxic T‐cell reactions.48 Several studies have found that HLA‐B*35:01 is associated with nevirapine‐induced cutaneous hypersensitivity in Caucasian, Asian, and Thai populations49 and that CD8+ and CD4+ T cells are implicated in this pathogenesis.50 One possibility is that the HLA‐B*35:01 antigens are directly or indirectly involved in the activation of T lymphocytes. The Allele Frequency Net Database (AFND) provides the scientific community with a freely available repository for the storage of immune gene frequencies in different worldwide populations. The apoptotic body, the focal lytic necrosis, and scattered lymphocytic infiltration are in the lobules (black arrow). © 2020 American Association for the Study of Liver Diseases. Based on current knowledge, the confounding contributions of these concomitantly used herbs and drugs to liver injury could be excluded. 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. An experienced histopathologist reviewed available liver biopsies. Users can contribute the results of their work into one common database and can perform database searches on information already available. HLA-net is an European network of the HLA diversity for histocompatibility, clinical transplantation, epidemiology and population genetics. We predicted classical HLA alleles using the Han‐MHC database as a reference panel. [7], https://en.wikipedia.org/w/index.php?title=HLA-DR2&oldid=821139487, Creative Commons Attribution-ShareAlike License, This page was last edited on 18 January 2018, at 17:09. We used chi‐squared or Fisher's exact test to compare genotype frequencies between groups. DPα and DPβ are encoded by two loci, HLA-DPA1 and HLA-DPB1, that are found in the MHC Class II (or HLA-D) region in the Human Leukocyte Antigen complex on human chromosome 6 (see protein boxes on right for links). The average hospitalization time of all patients was 19.9 ± 8.5 (9‐37) days. In this study, 27 gene loci were sequenced, including the classical HLA genes HLA‐A, HLA‐B, HLA‐C, HLA‐DPA1, HLA‐DPB1, HLA‐DQA1, HLA‐DQB1, and HLA‐DRB1; the nonclassical HLA genes HLA‐DMA, HLA‐DMB, HLA‐DOA, HLA‐DOB, HLA‐DRA1, HLA‐DRB3, HLA‐DRB4, HLA‐DRB5, HLA‐E, HLA‐F, HLA‐G, HLA‐H, HLA‐J, HLA‐K, and HLA‐L; and the non‐HLA genes MHC class I polypeptide‐related sequence A, MHC class I polypeptide‐related sequence B, transporter 1 adenosine triphosphate binding cassette subfamily B member, and transporter 2 adenosine triphosphate binding cassette subfamily B member. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. The sensitivity and specificity of the PM‐DILI clinical diagnosis were 88.5% and 87.9%, respectively. In any case, non Hardy–Weinberg frequencies should never be used as valid population estimates. The histological features of patients with PM‐associated DILI are shown in Fig. The Mann‐Whitney U test was used to determine whether two independent samples came from the same population. All participants were administered traditional Chinese herbal compound medicinal decoctions that mainly contain P. multiflorum radix, Atractylodes macrocephala rhizoma, Dioscoreae rhizoma, and Moutan cortex for tonifying the kidney and participated in a follow‐up examination between 2015 and 2016. A total of 37.5% (3/8) of HLA‐B*35:01 carriers showed asymptomatic transaminase elevation (relative risk, 8.0; 95% CI 1.2‐110.6; P < 0.02), compared with 4.7% (3/64) of noncarriers (Table 3). The sample size was calculated to detect a specified odds ratio (OR) >30, with a given power of 0.9 and a type I error of 0.05 with a module of tests for two proportions in PASS 15.19. Examples of the two most common injury patterns in patients with PM‐DILI (stained with hematoxylin and eosin). The Allele Frequency Net Database (AFND) provides the scientific community with a freely available repository for the storage of immune gene frequencies in different worldwide populations. A total of 230 subjects were enrolled based on eligibility criteria.16, 17 The overall study design is shown in Fig. All patients met one of the following predefined laboratory criteria: (1) aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) levels ≥5 times the upper limit of normal (ULN), (2) ALT or AST level ≥3 times ULN and total bilirubin level ≥2 ULN with clinically apparent jaundice, (3) serum alkaline phosphatase (ALP) level ≥2 times ULN, or (4) pathological diagnosis of liver injury. HLA‐B*35:01 is a common HLA‐B allele in Han Chinese, with a frequency of 2%‐5% according to the Allele Frequencies net database. 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. HLA‐B, which included 11 alleles, showed the greatest variation. The toxic components in PM and the mechanism linking HLA‐B*35:01 with PM‐DILI remain unknown. Information on the herbs or drugs used by all PM‐DILI patients is listed in Supporting Table S1. HLA We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) allele groups and alleles by PCR-SSP based typing in a total of 15,318 mixed ancestry Mexicans from all the states of the country divided into 78 sample sets, providing information regarding allelic and haplotypic frequencies and their linkage disequilibrium, as well as admixture estimates and genetic substructure. The frequencies of HLA‐B*35:01 were 45.4% in the patients; 2.7% in the Han‐MHC database, which consisted of 10,689 healthy control subjects18; and 2.8% in Chinese volunteers from the Chinese Bone Marrow Donor Program.23 In Fisher's exact test analysis, HLA‐B*35:01 (OR, 30.4; 95% CI, 11.7‐77.1; P = 1.91 × 10−10, after adjusting P = 2.37 × 10−8) was more significantly associated with PM‐DILI than were the other HLA alleles (Fig. ACG clinical guideline: the diagnosis and management of idiosyncratic drug‐induced liver injury, Guidelines for the diagnosis and management of herb‐induced liver injury, Deep sequencing of the MHC region in the Chinese population contributes to studies of complex disease, Power calculations for matched case‐control studies, Causality assessment in drug‐induced liver injury using a structured expert opinion process: comparison to the Roussel‐Uclaf Causality Assessment Method, HLA‐A, ‐B, and‐DRB1 polymorphism defined by sequence‐based typing of the Han population in northern China, Comprehensive, serologically equivalent DNA typing for HLA‐B by PCR using sequence‐specific primers (PCR‐SSP), High‐resolution analyses of human leukocyte antigens allele and haplotype frequencies based on 169,995 volunteers from the China Bone Marrow Donor Registry Program, Susceptibility to amoxicillin‐clavulanate‐induced liver injury is influenced by multiple HLA class I and II alleles, Hepatitis related to the Chinese medicine Shou‐wu‐pian manufactured from, CYP1A2 polymorphism in Chinese patients with acute liver injury induced by, Urine metabolomics study on the liver injury in rats induced by raw and processed, Hepatotoxicity in rats induced by aqueous extract of Polygoni Multiflori Radix, root of, Hepatotoxic assessment of Polygoni Multiflori Radix extract and toxicokinetic study of stilbene glucoside and anthraquinones in rats, HLA and delayed drug‐induced hypersensitivity, Classification of drug hypersensitivity into allergic, p‐i, and pseudo‐allergic forms, Pharmacogenomics of off‐target adverse drug reactions, HLA‐B*5701 testing to predict abacavir hypersensitivity, HLA‐B*5701 screening for hypersensitivity to abacavir, High sensitivity of human leukocyte antigen‐B*5701 as a marker for immunologically confirmed abacavir hypersensitivity in white and black patients, A genome‐wide study identifies HLA alleles associated with lumiracoxib‐related liver injury, HLA class II genotype influences the type of liver injury in drug‐induced idiosyncratic liver disease, HLA‐A*3101 and carbamazepine‐induced hypersensitivity reactions in Europeans, Genotype–phenotype association between HLA and carbamazepine‐induced hypersensitivity reactions: strength and clinical correlations, Genetic basis of drug‐induced liver injury: present and future, Human leukocyte antigen genetic risk factors of drug‐induced liver toxicology, Metabolomic study on immunological stress‐mediated the hepatotoxicity of, Human leukocyte antigen class I–restricted activation of CD8, HLA‐allelotype associations with nevirapine‐induced hypersensitivity reactions and hepatotoxicity: a systematic review of the literature and meta‐analysis.

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