title: Influence of IFNL3/4 polymorphisms on the incidence of cytomegalovirus infection after solid-organ transplantation.
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.
authors.affiliation: Infectious Diseases Service, Department of Medicine Transplantation Center, Department of Surgery.
authors.forename: Oriol
authors.initials: O
authors.lastname: Manuel
authors.affiliation: Infectious Diseases Service, Department of Medicine.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Wójtowicz
authors.affiliation: Infectious Diseases Service, Department of Medicine.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Bibert
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital, University of Zurich.
authors.forename: Nicolas J
authors.initials: NJ
authors.lastname: Mueller
authors.affiliation: Service of Transplantation, Department of Surgery, University Hospitals of Geneva.
authors.forename: Christian
authors.initials: C
authors.lastname: van Delden
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology Transplantation and Clinical Virology, Department Biomedicine (Haus Petersplatz), University of Basel.
authors.forename: Hans H
authors.initials: HH
authors.lastname: Hirsch
authors.affiliation: Clinic for Transplantation Immunology and Nephrology.
authors.forename: Juerg
authors.initials: J
authors.lastname: Steiger
authors.affiliation: Immunotherapy Laboratory, Department of Biomedicine.
authors.forename: Martin
authors.initials: M
authors.lastname: Stern
authors.affiliation: Clinical Microbiology, University Hospital Basel.
authors.forename: Adrian
authors.initials: A
authors.lastname: Egli
authors.affiliation: Department of Infectious Diseases, Inselspital, Bern University Hospital and University of Bern Clinic of Internal Medicine and Infectious Diseases, Clinica Luganese, Lugano.
authors.forename: Christian
authors.initials: C
authors.lastname: Garzoni
authors.affiliation: Division of Nephrology and Transplantation Medicine, Kantonsspital St. Gallen, Switzerland.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Binet
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology.
authors.forename: Maja
authors.initials: M
authors.lastname: Weisser
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Children's Hospital, Zurich.
authors.forename: Christoph
authors.initials: C
authors.lastname: Berger
authors.affiliation: Clinic of Internal Medicine and Infectious Diseases, Clinica Luganese, Lugano.
authors.forename: Alexia
authors.initials: A
authors.lastname: Cusini
authors.affiliation: Infectious Diseases Service, Department of Medicine Institute of Microbiology, University Hospital (CHUV) and University of Lausanne.
authors.forename: Pascal
authors.initials: P
authors.lastname: Meylan
authors.affiliation: Transplantation Center, Department of Surgery.
authors.forename: Manuel
authors.initials: M
authors.lastname: Pascual
authors.affiliation: Infectious Diseases Service, Department of Medicine.
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Bochud
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D003587:Cytomegalovirus / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000453:epidemiology / Q000235:genetics* / Q000517:prevention & control; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014779:Virus Replication; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C579163:IFNL4 protein, human
keywords: IL28B; antiviral immunity; cohort study; innate immunity; viral infection