IL-4 polymorphism influences susceptibility to Pneumocystis jirovecii pneumonia in HIV-positive patients.

Wójtowicz, Agnieszka; Bibert, Stéphanie; Taffé, Patrick; Bernasconi, Enos; Furrer, Hansjakob; Günthard, Huldrych F; Hoffmann, Matthias; Osthoff, Michael; Cavassini, Matthias; Bochud, Pierre-Yves (2019). IL-4 polymorphism influences susceptibility to Pneumocystis jirovecii pneumonia in HIV-positive patients. AIDS, 33(11), pp. 1719-1727. Lippincott Williams & Wilkins 10.1097/QAD.0000000000002283

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OBJECTIVES 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. DESIGN AND METHODS 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. RESULTS 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). CONCLUSION 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Infectiology

UniBE Contributor:

Furrer, Hansjakob

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0269-9370

Publisher:

Lippincott Williams & Wilkins

Language:

English

Submitter:

Andrea Flükiger-Flückiger

Date Deposited:

13 Aug 2019 11:37

Last Modified:

23 Oct 2019 02:36

Publisher DOI:

10.1097/QAD.0000000000002283

PubMed ID:

31225812

BORIS DOI:

10.7892/boris.131556

URI:

https://boris.unibe.ch/id/eprint/131556

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