Influence of IFNL3/4 polymorphisms on the incidence of cytomegalovirus infection after solid-organ transplantation

Manuel, Oriol; Wójtowicz, Agnieszka; Bibert, Stéphanie; Mueller, Nicolas J; van Delden, Christian; Hirsch, Hans H; Steiger, Juerg; Stern, Martin; Egli, Adrian; Garzoni, Christian; Binet, Isabelle; Weisser, Maja; Berger, Christoph; Cusini, Alexia; Meylan, Pascal; Pascual, Manuel; Bochud, Pierre-Yves; Swiss Transplant, Cohort Study; Huynh-Do, Uyen (2014). Influence of IFNL3/4 polymorphisms on the incidence of cytomegalovirus infection after solid-organ transplantation. Journal of infectious diseases, 211(6), pp. 906-914. Oxford University Press 10.1093/infdis/jiu557

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BACKGROUND

Polymorphisms in the interferon-λ (IFNL) 3/4 region have been associated with reduced hepatitis C virus clearance. We explored the role of such polymorphisms on the incidence of CMV infection in solid-organ transplant (SOT) recipients.

METHODS

Caucasian patients participating in the Swiss Transplant Cohort Study in 2008-2011 were included. A novel functional TT/-G polymorphism (rs368234815) in the CpG region upstream of IFNL3 was investigated.

RESULTS

A total of 840 SOT recipients at risk for CMV were included, among whom 373 (44%) received antiviral prophylaxis. The 12-months cumulative incidence of CMV replication and disease were 0.44 and 0.08, respectively. Patient homozygous for the minor rs368234815 allele (-G/-G) tended to have a higher cumulative incidence of CMV replication (SHR=1.30 [95%CI 0.97-1.74], P=0.07) compared to other patients (TT/TT or TT/-G). The association was significant among patients followed by a preemptive approach (SHR=1.46 [1.01-2.12], P=0.047), especially in patients receiving an organ from a seropositive donor (D+, SHR=1.92 [95%CI 1.30-2.85], P=0.001), but not among those who received antiviral prophylaxis (SHR=1.13 [95%CI 0.70-1.83], P=0.6). These associations remained significant in multivariate competing risk regression models.

CONCLUSIONS

Polymorphisms in the IFNL3/4 region influence susceptibility to CMV replication in SOT recipients, particularly in patients not receiving antiviral prophylaxis.

Item Type:

 Journal Article (Original Article)

Division/Institute:

 04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Nephrologie / Hypertonie
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Infectiology

UniBE Contributor:

 Garzoni, Christian, Cusini, Alexia, Huynh-Do, Uyen

Subjects:

 600 Technology > 610 Medicine & health

ISSN:

 0022-1899

Publisher:

 Oxford University Press

Language:

 English

Submitter:

 Annelies Luginbühl

Date Deposited:

 04 Dec 2014 14:01

Last Modified:

 05 Dec 2022 14:37

Publisher DOI:

 10.1093/infdis/jiu557

PubMed ID:

 25301956

Additional Information:

Swiss Transplant Cohort Study: nur Berner Autoren namentlich erwähnt

BORIS DOI:

 10.7892/boris.59914

URI:

 https://boris.unibe.ch/id/eprint/59914

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