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

Publication

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

Journal Paper/Review - Oct 9, 2014

Manuel Oriol, Swiss Transplant Cohort Study (STCS), Bochud Pierre-Yves, Pascual Manuel, Meylan Pascal, Cusini Alexia, Christoph Berger, Maja Weisser, Binet Françoise-Isabelle, Garzoni Christian, Egli Adrian, Stern Martin, Steiger Juerg, Hirsch Hans H, Van Delden Christian, Mueller Nicolas J, Bibert Stéphanie, Wójtowicz Agnieszka, Swiss Transplant Cohort Study STCS

Citation

Manuel O, Swiss Transplant Cohort Study (STCS), Bochud P, Pascual M, Meylan P, Cusini A, Christoph B, Maja W, Binet F, Garzoni C, Egli A, Stern M, Steiger J, Hirsch H, Van Delden C, Mueller N, Bibert S, Wójtowicz A, Swiss Transplant Cohort Study STCS. Influence of IFNL3/4 Polymorphisms on the Incidence of Cytomegalovirus Infection After Solid-Organ Transplantation. J Infect Dis 2014; 211:906-14.

Type

Journal Paper/Review (English)

Journal

J Infect Dis 2014; 211

Publication Date

Oct 9, 2014

Issn Electronic

1537-6613

Pages

906-14

Brief description/objective

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.