Influence of IFNL3/4 polymorphisms on the incidence of cytomegalovirus infection after solid-organ transplantation.
- Manuel O Infectious Diseases Service, Department of Medicine Transplantation Center, Department of Surgery.
- Wójtowicz A Infectious Diseases Service, Department of Medicine.
- Bibert S Infectious Diseases Service, Department of Medicine.
- Mueller NJ Division of Infectious Diseases and Hospital Epidemiology, University Hospital, University of Zurich.
- van Delden C Service of Transplantation, Department of Surgery, University Hospitals of Geneva.
- Hirsch HH Division of Infectious Diseases and Hospital Epidemiology Transplantation and Clinical Virology, Department Biomedicine (Haus Petersplatz), University of Basel.
- Steiger J Clinic for Transplantation Immunology and Nephrology.
- Stern M Immunotherapy Laboratory, Department of Biomedicine.
- Egli A Clinical Microbiology, University Hospital Basel.
- Garzoni C Department of Infectious Diseases, Inselspital, Bern University Hospital and University of Bern Clinic of Internal Medicine and Infectious Diseases, Clinica Luganese, Lugano.
- Binet I Division of Nephrology and Transplantation Medicine, Kantonsspital St. Gallen, Switzerland.
- Weisser M Division of Infectious Diseases and Hospital Epidemiology.
- Berger C Division of Infectious Diseases and Hospital Epidemiology, University Children's Hospital, Zurich.
- Cusini A Clinic of Internal Medicine and Infectious Diseases, Clinica Luganese, Lugano.
- Meylan P Infectious Diseases Service, Department of Medicine Institute of Microbiology, University Hospital (CHUV) and University of Lausanne.
- Pascual M Transplantation Center, Department of Surgery.
- Bochud PY Infectious Diseases Service, Department of Medicine.
- 2014-10-11
Published in:
- The Journal of infectious diseases. - 2015
IL28B
antiviral immunity
cohort study
innate immunity
viral infection
Adult
Aged
Antiviral Agents
Cytomegalovirus
Cytomegalovirus Infections
Female
Genetic Association Studies
Genetic Predisposition to Disease
Humans
Incidence
Interferons
Interleukins
Kidney Transplantation
Male
Middle Aged
Polymorphism, Single Nucleotide
Virus Replication
English
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.
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.
- Language
-
- English
- Open access status
- bronze
- Identifiers
-
- DOI 10.1093/infdis/jiu557
- PMID 25301956
- Persistent URL
- https://sonar.ch/global/documents/93196
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