ID

45768

Description

Principal Investigator: Lauren A. Trepanier, DVM, PhD, University of Wisconsin-Madison, School of Veterinary Medicine, Madison, WI, USA MeSH: Drug Hypersensitivity Syndrome https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001124 Hypersensitivity (HS) reactions to sulfonamide antibiotics occur uncommonly, but with potentially severe clinical manifestations. A familial predisposition to sulfonamide HS is suspected, but robust predictive genetic risk factors have yet to be identified. Strongly linked genetic polymorphisms have been used clinically as screening tests for other HS reactions prior to administration of high-risk drugs. The purpose of this study was to evaluate for genetic risk of sulfonamide HS in the immunocompetent population using genome-wide association. Ninety-one patients with symptoms after trimethoprim-sulfamethoxazole (TMP-SMX) attributable to "probable" drug HS based on medical record review and the Naranjo Adverse Drug Reaction Probability Scale, and 184 age- and sex-matched patients who tolerated a therapeutic course of TMP-SMX, were included in a genome-wide association study using both common and rare variant techniques. Additionally, two subgroups of HS patients with a more refined clinical phenotype (fever and rash; or fever, rash and eosinophilia) were evaluated separately. For the full dataset, no single nucleotide polymorphisms were suggestive of or reached genome-wide significance in the common variant analysis, nor was any genetic locus significant in the rare variant analysis. A single, possible gene locus association (*COL12A1*) was identified in the rare variant analysis for patients with both fever and rash, but the sample size was very small in this subgroup (n=16), and this may be a false positive finding. No other significant associations were found for the subgroups. No convincing genetic risk factors for sulfonamide HS were identified in this population. These negative findings may be due to challenges in accurately confirming the phenotype in exanthematous drug eruptions, or to unidentified gene-environment interactions influencing sulfonamide HS. Reprinted under PLOS ONE's open access license, CC-BY (http://www.plos.org/open-access).

Lien

dbGaP-study=phs001124

Mots-clés

  1. 19/06/2023 19/06/2023 - Chiara Middel
Détendeur de droits

Lauren A. Trepanier, DVM, PhD, University of Wisconsin-Madison, School of Veterinary Medicine, Madison, WI, USA

Téléchargé le

19 juin 2023

DOI

Pour une demande vous connecter.

Licence

Creative Commons BY 4.0

Modèle Commentaires :

Ici, vous pouvez faire des commentaires sur le modèle. À partir des bulles de texte, vous pouvez laisser des commentaires spécifiques sur les groupes Item et les Item.

Groupe Item commentaires pour :

Item commentaires pour :

Vous devez être connecté pour pouvoir télécharger des formulaires. Veuillez vous connecter ou s’inscrire gratuitement.

dbGaP phs001124 Mechanisms of Risk for Sulfonamide Hypersensitivity

Eligibility Criteria

Inclusion and exclusion criteria
Description

Inclusion and exclusion criteria

Alias
UMLS CUI [1,1]
C1512693
UMLS CUI [1,2]
C0680251
*CASES*
Description

Elig.phs001124.v1.p1.1

Type de données

boolean

Alias
UMLS CUI [1,1]
C1706256
Inclusion:
Description

Elig.phs001124.v1.p1.2

Type de données

boolean

Alias
UMLS CUI [1,1]
C1512693
Administration of TMP-SMX for at least 5 days prior to the adverse event
Description

Elig.phs001124.v1.p1.3

Type de données

boolean

Alias
UMLS CUI [1,1]
C1533734
UMLS CUI [1,2]
C0041044
UMLS CUI [1,3]
C0449238
UMLS CUI [1,4]
C0332152
UMLS CUI [1,5]
C0877248
Documentation of one or more new clinical signs after starting TMP-SMX, including fever with or without eosinophilia, skin rash, increases in liver enzyme activities, hyperbilirubinemia, blood dyscrasias (anemia, leukopenia or thrombocytopenia), pneumonitis, myocarditis, aseptic meningitis, polyarthritis, acute interstitial nephritis, toxic epidermal necrolysis, or Stevens-Johnson syndrome
Description

Elig.phs001124.v1.p1.4

Type de données

boolean

Alias
UMLS CUI [1,1]
C0920316
UMLS CUI [1,2]
C0205314
UMLS CUI [1,3]
C0037088
UMLS CUI [1,4]
C0332282
UMLS CUI [1,5]
C0041044
UMLS CUI [1,6]
C0015967
UMLS CUI [1,7]
C2240374
UMLS CUI [1,8]
C0015230
UMLS CUI [1,9]
C0857093
UMLS CUI [1,10]
C0020433
UMLS CUI [1,11]
C0018939
UMLS CUI [1,12]
C0002871
UMLS CUI [1,13]
C0023530
UMLS CUI [1,14]
C0040034
UMLS CUI [1,15]
C3714636
UMLS CUI [1,16]
C0027059
UMLS CUI [1,17]
C0025290
UMLS CUI [1,18]
C0162323
UMLS CUI [1,19]
C1843274
UMLS CUI [1,20]
C0014518
UMLS CUI [1,21]
C0038325
Lack of other clinical explanation for the adverse event
Description

Elig.phs001124.v1.p1.5

Type de données

boolean

Alias
UMLS CUI [1,1]
C0332197
UMLS CUI [1,2]
C0205394
UMLS CUI [1,3]
C0205210
UMLS CUI [1,4]
C0681841
UMLS CUI [1,5]
C0877248
Resolution of clinical signs with discontinuation of TMP-SMX alone
Description

Elig.phs001124.v1.p1.6

Type de données

boolean

Alias
UMLS CUI [1,1]
C2699488
UMLS CUI [1,2]
C0205210
UMLS CUI [1,3]
C0037088
UMLS CUI [1,4]
C0457454
UMLS CUI [1,5]
C0041044
Exclusion:
Description

Elig.phs001124.v1.p1.7

Type de données

boolean

Alias
UMLS CUI [1,1]
C0680251
Gastrointestinal symptoms such as nausea, vomiting or diarrhea, in absence of other symptoms described above
Description

Elig.phs001124.v1.p1.8

Type de données

boolean

Alias
UMLS CUI [1,1]
C0426576
UMLS CUI [1,2]
C0027497
UMLS CUI [1,3]
C0042963
UMLS CUI [1,4]
C0011991
UMLS CUI [2,1]
C0332197
UMLS CUI [2,2]
C0205394
UMLS CUI [2,3]
C1457887
UMLS CUI [2,4]
C0678257
Acute anaphylactoid reactions were excluded
Description

Elig.phs001124.v1.p1.9

Type de données

boolean

Alias
UMLS CUI [1,1]
C0680251
UMLS CUI [1,2]
C0001314
UMLS CUI [1,3]
C0340865
Immunocompromised patients, including those with HIV infection or undergoing immunosuppressive chemotherapy
Description

Elig.phs001124.v1.p1.10

Type de données

boolean

Alias
UMLS CUI [1,1]
C4048329
UMLS CUI [1,2]
C0019693
UMLS CUI [1,3]
C0521116
UMLS CUI [1,4]
C0021081
UMLS CUI [1,5]
C0392920
*CONTROLS*
Description

Elig.phs001124.v1.p1.11

Type de données

boolean

Alias
UMLS CUI [1,1]
C0009932
Inclusion:
Description

Elig.phs001124.v1.p1.12

Type de données

boolean

Alias
UMLS CUI [1,1]
C1512693
Administration of a course of TMP-SMX at a standard therapeutic daily dosage for at least 10 days, with adequate follow-up in the medical record to indicate that the drug was taken and tolerated without adverse event.
Description

Elig.phs001124.v1.p1.13

Type de données

boolean

Alias
UMLS CUI [1,1]
C1533734
UMLS CUI [1,2]
C1442989
UMLS CUI [1,3]
C0087111
UMLS CUI [1,4]
C2348070
UMLS CUI [1,5]
C0041044
UMLS CUI [1,6]
C0449238
UMLS CUI [1,7]
C0205411
UMLS CUI [1,8]
C1522577
UMLS CUI [1,9]
C0025102
UMLS CUI [1,10]
C1512806
UMLS CUI [1,11]
C0013227
UMLS CUI [1,12]
C0013220
UMLS CUI [1,13]
C0332288
UMLS CUI [1,14]
C0877248

Similar models

Eligibility Criteria

Name
Type
Description | Question | Decode (Coded Value)
Type de données
Alias
Item Group
Inclusion and exclusion criteria
C1512693 (UMLS CUI [1,1])
C0680251 (UMLS CUI [1,2])
Elig.phs001124.v1.p1.1
Item
*CASES*
boolean
C1706256 (UMLS CUI [1,1])
Elig.phs001124.v1.p1.2
Item
Inclusion:
boolean
C1512693 (UMLS CUI [1,1])
Elig.phs001124.v1.p1.3
Item
Administration of TMP-SMX for at least 5 days prior to the adverse event
boolean
C1533734 (UMLS CUI [1,1])
C0041044 (UMLS CUI [1,2])
C0449238 (UMLS CUI [1,3])
C0332152 (UMLS CUI [1,4])
C0877248 (UMLS CUI [1,5])
Elig.phs001124.v1.p1.4
Item
Documentation of one or more new clinical signs after starting TMP-SMX, including fever with or without eosinophilia, skin rash, increases in liver enzyme activities, hyperbilirubinemia, blood dyscrasias (anemia, leukopenia or thrombocytopenia), pneumonitis, myocarditis, aseptic meningitis, polyarthritis, acute interstitial nephritis, toxic epidermal necrolysis, or Stevens-Johnson syndrome
boolean
C0920316 (UMLS CUI [1,1])
C0205314 (UMLS CUI [1,2])
C0037088 (UMLS CUI [1,3])
C0332282 (UMLS CUI [1,4])
C0041044 (UMLS CUI [1,5])
C0015967 (UMLS CUI [1,6])
C2240374 (UMLS CUI [1,7])
C0015230 (UMLS CUI [1,8])
C0857093 (UMLS CUI [1,9])
C0020433 (UMLS CUI [1,10])
C0018939 (UMLS CUI [1,11])
C0002871 (UMLS CUI [1,12])
C0023530 (UMLS CUI [1,13])
C0040034 (UMLS CUI [1,14])
C3714636 (UMLS CUI [1,15])
C0027059 (UMLS CUI [1,16])
C0025290 (UMLS CUI [1,17])
C0162323 (UMLS CUI [1,18])
C1843274 (UMLS CUI [1,19])
C0014518 (UMLS CUI [1,20])
C0038325 (UMLS CUI [1,21])
Elig.phs001124.v1.p1.5
Item
Lack of other clinical explanation for the adverse event
boolean
C0332197 (UMLS CUI [1,1])
C0205394 (UMLS CUI [1,2])
C0205210 (UMLS CUI [1,3])
C0681841 (UMLS CUI [1,4])
C0877248 (UMLS CUI [1,5])
Elig.phs001124.v1.p1.6
Item
Resolution of clinical signs with discontinuation of TMP-SMX alone
boolean
C2699488 (UMLS CUI [1,1])
C0205210 (UMLS CUI [1,2])
C0037088 (UMLS CUI [1,3])
C0457454 (UMLS CUI [1,4])
C0041044 (UMLS CUI [1,5])
Elig.phs001124.v1.p1.7
Item
Exclusion:
boolean
C0680251 (UMLS CUI [1,1])
Elig.phs001124.v1.p1.8
Item
Gastrointestinal symptoms such as nausea, vomiting or diarrhea, in absence of other symptoms described above
boolean
C0426576 (UMLS CUI [1,1])
C0027497 (UMLS CUI [1,2])
C0042963 (UMLS CUI [1,3])
C0011991 (UMLS CUI [1,4])
C0332197 (UMLS CUI [2,1])
C0205394 (UMLS CUI [2,2])
C1457887 (UMLS CUI [2,3])
C0678257 (UMLS CUI [2,4])
Elig.phs001124.v1.p1.9
Item
Acute anaphylactoid reactions were excluded
boolean
C0680251 (UMLS CUI [1,1])
C0001314 (UMLS CUI [1,2])
C0340865 (UMLS CUI [1,3])
Elig.phs001124.v1.p1.10
Item
Immunocompromised patients, including those with HIV infection or undergoing immunosuppressive chemotherapy
boolean
C4048329 (UMLS CUI [1,1])
C0019693 (UMLS CUI [1,2])
C0521116 (UMLS CUI [1,3])
C0021081 (UMLS CUI [1,4])
C0392920 (UMLS CUI [1,5])
Elig.phs001124.v1.p1.11
Item
*CONTROLS*
boolean
C0009932 (UMLS CUI [1,1])
Elig.phs001124.v1.p1.12
Item
Inclusion:
boolean
C1512693 (UMLS CUI [1,1])
Elig.phs001124.v1.p1.13
Item
Administration of a course of TMP-SMX at a standard therapeutic daily dosage for at least 10 days, with adequate follow-up in the medical record to indicate that the drug was taken and tolerated without adverse event.
boolean
C1533734 (UMLS CUI [1,1])
C1442989 (UMLS CUI [1,2])
C0087111 (UMLS CUI [1,3])
C2348070 (UMLS CUI [1,4])
C0041044 (UMLS CUI [1,5])
C0449238 (UMLS CUI [1,6])
C0205411 (UMLS CUI [1,7])
C1522577 (UMLS CUI [1,8])
C0025102 (UMLS CUI [1,9])
C1512806 (UMLS CUI [1,10])
C0013227 (UMLS CUI [1,11])
C0013220 (UMLS CUI [1,12])
C0332288 (UMLS CUI [1,13])
C0877248 (UMLS CUI [1,14])

Utilisez ce formulaire pour les retours, les questions et les améliorations suggérées.

Les champs marqués d’un * sont obligatoires.

Do you need help on how to use the search function? Please watch the corresponding tutorial video for more details and learn how to use the search function most efficiently.

Watch Tutorial