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Oriol Manuel, Agnieszka Wójtowicz, Stéphanie Bibert, Nicolas J. Mueller, Christian van Delden, Hans H. Hirsch, Juerg Steiger, Martin Stern, Adrian Egli, Christian Garzoni, Isabelle Binet, Maja Weisser, Christoph Berger, Alexia Cusini, Pascal Meylan, Manuel Pascual, Pierre-Yves Bochud, Swiss Transplant Cohort Study (STCS), Influence of IFNL3/4 Polymorphisms on the Incidence of Cytomegalovirus Infection After Solid-Organ Transplantation, The Journal of Infectious Diseases, Volume 211, Issue 6, 15 March 2015, Pages 906–914, https://doi.org/10.1093/infdis/jiu557
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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.
