Evidence map›Paper›PMID 32270503›Full record

ArticleHepatology (Baltimore, Md.)2021

Human Leukocyte Antigen B*14:01 and B*35:01 Are Associated With Trimethoprim-Sulfamethoxazole Induced Liver Injury.

Yi-Ju Li, Elizabeth J Phillips, Andrew Dellinger, Paola Nicoletti, Ryan Schutte, Danmeng Li, David A Ostrov, Robert J Fontana, Paul B Watkins, Andrew Stolz and 5 more

Open access · greenAbstract read
In one paragraph

Article in Hepatology (Baltimore, Md.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
7.6field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

47 citing papers in PubMed, 67 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Liver Injury From Medications Used for Treating Inflammatory Bowel Disease: The Drug-Induced Liver Injury Network Experience.Liver international : official journal of the International Association for the Study of the Liver · 2026
    Article
  6. Article
  7. Article
  8. Review
  9. Human Leukocyte Antigen (International journal of molecular sciences · 2026
    Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Liver Injury due to Intravenous Methylprednisolone in the Drug-Induced Liver Injury Network.Liver international : official journal of the International Association for the Study of the Liver · 2025
    Article
  18. Genetic Variants of GBP4: Reduced Risks for Drug-Induced Acute Liver Failure in Non-Finnish European Population.Liver international : official journal of the International Association for the Study of the Liver · 2025
    Article
  19. Genetic and Genomic Approaches to the Study of Drug-Induced Liver Injury.Liver international : official journal of the International Association for the Study of the Liver · 2025
    Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 11 institutions in 2 countries.

Yi-Ju LiDepartment of Biostatistics and Bioinformatics, Duke University Medical Center, Duke University, Durham, NC.ORCID 0000-0001-6996-4834
Elizabeth J PhillipsDepartment of Medicine, Vanderbilt University Medical School and School of Medicine Vanderbilt University, Nashville, TN.ORCID 0000-0002-7623-3383
Andrew DellingerMolecular Physiology Institute, Duke University Medical Center, Duke University, Durham, NC.ORCID 0000-0003-1650-4329
Paola NicolettiDepartment of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, New York, NY.
Ryan SchutteDepartment of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL.
Danmeng LiDepartment of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL.
David A OstrovDepartment of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL.
Robert J FontanaDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI.
Paul B WatkinsDivision of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC.
Andrew StolzDivision of Gastroenterology and Hepatology, Keck School of Medicine, University of Southern California, Los Angeles, CA.
Ann K DalyInstitute of Translational and Clinical Research, Newcastle University, Newcastle Upon Tyne, United Kingdom.
Guruprasad P AithalNottingham Digestive Diseases Centre, Nottingham University Hospital National Health Service Trust and University of Nottingham, Nottingham, United Kingdom.
Huiman BarnhartDepartment of Biostatistics and Bioinformatics, Duke University Medical Center, Duke University, Durham, NC.
Naga ChalasaniDivision of Gastroenterology and Hepatology, School of Medicine, Indiana University, Indianapolis, IN.
Drug-induced Liver Injury Network
University of Florida · USDuke University · USDuke Medical Center · USIndiana University – Purdue University Indianapolis · USMount Sinai Health System · USNational Health Service · GBNewcastle University · GBUniversity of Michigan · USUniversity of North Carolina at Chapel Hill · USUniversity of Southern California · USVanderbilt University · US

Funding

Furthering scientific understanding of mechanisms underlying resilience to the effects of AD pathology by incorporating state of the art quantification of gliosis, inflammation, & synaptic toxicityU01AG006781 · NIA · UNIVERSITY OF WASHINGTON · PI CRANE, PAUL K, LARSON, ERIC B · 1986 to 2020
$39.3M
Drug Induced Liver Injury Network Data Coordinating CenterU01DK065176 · NIDDK · DUKE UNIVERSITY · PI Huiman X Barnhart · 2003 to 2026
$25.5M
JH/CIDR Genotyping for Genome-Wide Association StudiesU01HG004438 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2007 to 2011
$24.2M
A Center for GEI Association StudiesU01HG004424 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY · 2007 to 2010
$21.4M
Coordinating Center for the Drug Induced Liver Injury Network (DILIN)U24DK065176 · NIDDK · DUKE UNIVERSITY · PI BARNHART, HUIMAN X · 2018 to 2022
$7.6M
IU Clinical Center: Drug Induced Liver Injury NetworkU01DK065211 · NIDDK · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI NAGA P CHALASANI · 2003 to 2026
$7.5M
University of North Carolina Clinical Center for DILINU01DK065201 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI PAUL B WATKINS · 2003 to 2026
$7.3M
Vanderbilt Genome-Electronic Records ProjectU01HG004603 · NHGRI · VANDERBILT UNIVERSITY · PI RODEN, DAN M · 2007 to 2011
$7.3M
Michigan Hepatotoxicity Clinical Research Network Renewal 2018U01DK065184 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ROBERT J FONTANA · 2003 to 2026
$7.0M
The Drug Induced Liver Injury Network (DILIN): Focus on Herbal and DietarySupplementsU01DK083027 · NIDDK · THOMAS JEFFERSON UNIVERSITY · PI Dina Halegoua-DeMarzio · 2008 to 2026
$7.0M
USC-UCLA Drug-Induced Liver Injury (DILI) Clinical Center.U01DK083020 · NIDDK · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Lily Dara · 2008 to 2026
$5.9M
Mount Sinai Regional Drug Induced Liver Injury Network SiteU01DK100928 · NIDDK · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI AHMAD, JAWAD, ODIN, JOSEPH · 2013 to 2022
$4.0M
NHGRI NIH HHS U01 HG004424NHGRI NIH HHS U01 HG004438NHGRI NIH HHS U01 HG004603NHGRI NIH HHS U01 HG004608NHGRI NIH HHS U01 HG007417NIA NIH HHS U01 AG006781NIDDK NIH HHS U01 DK065176NIDDK NIH HHS U01 DK065184NIDDK NIH HHS U01 DK065193NIDDK NIH HHS U01-DK065193NIDDK NIH HHS U01 DK065201NIDDK NIH HHS U01 DK065211NIDDK NIH HHS U01 DK065238NIDDK NIH HHS U01 DK082992NIDDK NIH HHS U01 DK083020NIDDK NIH HHS U01 DK083023NIDDK NIH HHS U01 DK083027NIDDK NIH HHS U01 DK100928NIDDK NIH HHS U24 DK065176
6 · The paper itself

Abstract

BACKGROUND AND

aimsTrimethoprim (TMP)-sulfamethoxazole (SMX) is an important cause of idiosyncratic drug-induced liver injury (DILI), but its genetic risk factors are not well understood. This study investigated the relationship between variants in the human leukocyte antigen (HLA) class 1 and 2 genes and well-characterized cases of TMP-SMX DILI. APPROACH AND

resultsEuropean American and African American persons with TMP-SMX DILI were compared with respective population controls. HLA sequencing was performed by Illumina MiSeq (Illumina, San Diego, CA) for cases. The HLA genotype imputation with attribute bagging program was used to impute HLA alleles for controls. The allele frequency difference between case patients and controls was tested by Fisher's exact tests for each ethnic group. For European Americans, multivariable logistic regression with Firth penalization was used to test the HLA allelic effect after adjusting for age and the top two principal components. Molecular docking was performed to assess HLA binding with TMP and SMX. The European American subset had 51 case patients and 12,156 controls, whereas the African American subset had 10 case patients and 5,439 controls. Four HLA alleles were significantly associated in the European American subset, with HLA-B*14:01 ranking at the top (odds ratio, 9.20; 95% confidence interval, 3.16, 22.35; P = 0.0003) after covariate adjustment. All carriers of HLA-B*14:01 with TMP-SMX DILI possessed HLA-C*08:02, another significant allele (P = 0.0026). This pattern was supported by HLA-B*14:01-HLA-C*08:02 haplotype association (P = 1.33 × 10

conclusionsHLA-B*14:01 is associated with TMP-SMX DILI in European Americans, and HLA-B*35:01 may be a potential genetic risk factor for African Americans.

Indexed as

AdultAgedAllelesBlack or African AmericanChemical and Drug Induced Liver InjuryFemaleGenome-Wide Association StudyHaplotypesHLA-B AntigensHumansLogistic ModelsMaleMiddle AgedMolecular Docking SimulationMultivariate AnalysisTrimethoprim, Sulfamethoxazole Drug CombinationHLA-B AntigensTrimethoprim, Sulfamethoxazole Drug Combination

Identifiers

PMID32270503
PMCPMC7544638
OpenAlexW3015665353

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.