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J Infect Dis. 2015 Mar 15;211(6):906-14. doi: 10.1093/infdis/jiu557. Epub 2014 Oct 9.

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

Author information

1
Infectious Diseases Service, Department of Medicine Transplantation Center, Department of Surgery.
2
Infectious Diseases Service, Department of Medicine.
3
Division of Infectious Diseases and Hospital Epidemiology, University Hospital, University of Zurich.
4
Service of Transplantation, Department of Surgery, University Hospitals of Geneva.
5
Division of Infectious Diseases and Hospital Epidemiology Transplantation and Clinical Virology, Department Biomedicine (Haus Petersplatz), University of Basel.
6
Clinic for Transplantation Immunology and Nephrology.
7
Immunotherapy Laboratory, Department of Biomedicine.
8
Clinical Microbiology, University Hospital Basel.
9
Department of Infectious Diseases, Inselspital, Bern University Hospital and University of Bern Clinic of Internal Medicine and Infectious Diseases, Clinica Luganese, Lugano.
10
Division of Nephrology and Transplantation Medicine, Kantonsspital St. Gallen, Switzerland.
11
Division of Infectious Diseases and Hospital Epidemiology.
12
Division of Infectious Diseases and Hospital Epidemiology, University Children's Hospital, Zurich.
13
Clinic of Internal Medicine and Infectious Diseases, Clinica Luganese, Lugano.
14
Infectious Diseases Service, Department of Medicine Institute of Microbiology, University Hospital (CHUV) and University of Lausanne.
15
Transplantation Center, Department of Surgery.

Abstract

BACKGROUND:

Polymorphisms in IFNL3 and IFNL4, the genes encoding interferon λ3 and interferon λ4, respectively, have been associated with reduced hepatitis C virus clearance. We explored the role of such polymorphisms on the incidence of cytomegalovirus (CMV) infection in solid-organ transplant recipients.

METHODS:

White 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 solid-organ transplant recipients at risk for CMV infection were included, among whom 373 (44%) received antiviral prophylaxis. The 12-month cumulative incidence of CMV replication and disease were 0.44 and 0.08 cases, respectively. Patient homozygous for the minor rs368234815 allele (-G/-G) tended to have a higher cumulative incidence of CMV replication (subdistribution hazard ratio [SHR], 1.30 [95% confidence interval {CI}, .97-1.74]; P = .07), compared with other patients (TT/TT or TT/-G). The association was significant among patients followed by a preemptive approach (SHR, 1.46 [95% CI, 1.01-2.12]; P = .047), especially in patients receiving an organ from a seropositive donor (SHR, 1.92 [95% CI, 1.30-2.85]; P = .001), but not among those who received antiviral prophylaxis (SHR, 1.13 [95% CI, .70-1.83]; P = .6). These associations remained significant in multivariate competing risk regression models.

CONCLUSIONS:

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

KEYWORDS:

IL28B; antiviral immunity; cohort study; innate immunity; viral infection

PMID:
25301956
DOI:
10.1093/infdis/jiu557
[Indexed for MEDLINE]
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