Titre
IL-4 polymorphism influences susceptibility to Pneumocystis jirovecii pneumonia in HIV-positive patients.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Wójtowicz, A.
Auteure/Auteur
Bibert, S.
Auteure/Auteur
Taffé, P.
Auteure/Auteur
Bernasconi, E.
Auteure/Auteur
Furrer, H.
Auteure/Auteur
Günthard, H.F.
Auteure/Auteur
Hoffmann, M.
Auteure/Auteur
Osthoff, M.
Auteure/Auteur
Cavassini, M.
Auteure/Auteur
Bochud, P.Y.
Auteure/Auteur
Groupes de travail
Swiss HIV Cohort Study
Liens vers les personnes
Liens vers les unités
ISSN
1473-5571
Statut éditorial
Publié
Date de publication
2019-09
Volume
33
Numéro
11
Première page
1719
Dernière page/numéro d’article
1727
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Résumé
Pneumocystis jirovecii pneumonia (PJP) is an important cause of morbidity and mortality in HIV-positive patients. Polymorphisms in immune genes are increasingly reported to influence susceptibility to fungal infections. We analysed the role of 21 single nucleotide polymorphisms from 19 candidate genes on PJP development in patients from the Swiss HIV Cohort Study.
The analysis included patients with a nadir CD4 T-cell count less than 200 cells/μl, divided into a discovery (N = 1645) and a replication (N = 1861) cohort. The associations were analysed by using cumulative incidence curves as well as competing risk regression over 18 years, starting from the estimated date of HIV infection, considering death a competing risk, with censoring at lost follow-up, and assuming the dominant mode of inheritance.
The minor allele of rs2243250 in IL-4 was associated with the risk of PJP in the discovery cohort (cumulative incidence 0.18 versus 0.12, P = 0.002). This association was replicated in the validation cohort (0.16 versus 0.12, P = 0.02). It was still significant in multivariate models, adjusted for HIV transmission mode, viral load, CD4 T cells slope, age, antiretroviral therapy, tobacco smoking, hepatitis C virus coinfection, year of cohort entry and PJP prophylaxis (global subhazard ratio 1.42, 95% confidence interval 1.17-1.73, P = 0.0004).
Our data suggest rs2243250, a single nucleotide polymorphism known to influence IL-4 production, is associated with susceptibility to PJP in HIV-positive patients.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.
The analysis included patients with a nadir CD4 T-cell count less than 200 cells/μl, divided into a discovery (N = 1645) and a replication (N = 1861) cohort. The associations were analysed by using cumulative incidence curves as well as competing risk regression over 18 years, starting from the estimated date of HIV infection, considering death a competing risk, with censoring at lost follow-up, and assuming the dominant mode of inheritance.
The minor allele of rs2243250 in IL-4 was associated with the risk of PJP in the discovery cohort (cumulative incidence 0.18 versus 0.12, P = 0.002). This association was replicated in the validation cohort (0.16 versus 0.12, P = 0.02). It was still significant in multivariate models, adjusted for HIV transmission mode, viral load, CD4 T cells slope, age, antiretroviral therapy, tobacco smoking, hepatitis C virus coinfection, year of cohort entry and PJP prophylaxis (global subhazard ratio 1.42, 95% confidence interval 1.17-1.73, P = 0.0004).
Our data suggest rs2243250, a single nucleotide polymorphism known to influence IL-4 production, is associated with susceptibility to PJP in HIV-positive patients.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.
PID Serval
serval:BIB_8B200C547F87
PMID
Date de création
2019-06-27T15:00:37.383Z
Date de création dans IRIS
2025-05-20T21:00:53Z
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Nom
31225812_BIB_8B200C547F87.pdf
Version du manuscrit
published
Licence
https://creativecommons.org/licenses/by-nc-nd/4.0
Taille
271.28 KB
Format
Adobe PDF
PID Serval
serval:BIB_8B200C547F87.P001
URN
urn:nbn:ch:serval-BIB_8B200C547F877
Somme de contrôle
(MD5):9566a641dfc1ae56e78b123270774932