Influence of IFNL3/4 Polymorphisms on the Incidence of Cytomegalovirus Infection After Solid-Organ Transplantation

O Manuel, A Wójtowicz, S Bibert… - The Journal of …, 2015 - academic.oup.com
O Manuel, A Wójtowicz, S Bibert, NJ Mueller, C van Delden, HH Hirsch, J Steiger, M Stern
The Journal of infectious diseases, 2015academic.oup.com
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 …
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.
Oxford University Press