Impacts of Interleukin-18 Polymorphisms on the Incidence of Delayed-Onset Cytomegalovirus Infection in a Cohort of Kidney Transplant Recipients

Abstract

Background: The incidence of cytomegalovirus (CMV) infection in solid organ transplant recipients may be reduced by antiviral prophylaxis, but this strategy may lead to delayed-onset CMV infection. The proinflammatory cytokine interleukin (IL)-18 plays a major role in viral host defense responses. This study examines the impacts of 2 single-nucleotide polymorphisms (SNPs) in the promoter region of the IL-18 gene,-607C/A (rs1946518) and-137G/C (rs187238), on the incidence of delayed-onset CMV infection in patients undergoing kidney transplant. Methods: This retrospective study analyzed 2 IL-18 SNPs in consecutive adult kidney transplant recipients using real-time polymerase chain reaction with TaqMan probes. Participants were enrolled over the period 2005-2013 and stratified according to their IL-18 SNP genotype. The concordance index (Harrell's c-index) was used as a measure of the discriminatory power of the predictive models constructed with bootstrapping to correct for optimistic bias. Results: Seven hundred nine patients received transplants in the study period, and 498 met selection criteria. Cytomegalovirus infection and disease incidence were 38% and 7.5%, respectively. In multivariate competing risk regression models, carriers of the-607C/-137G haplotype who received prophylaxis showed a higher incidence of CMV replication after antiviral agent discontinuation (hazard ratio = 2.42 [95% confidence interval, 1.11-5.26]; P =. 026), whereas CMV disease was not observed in those given prophylaxis who were noncarriers of this polymorphism (P =. 009). Conclusions: Our findings suggest that the-607C/-137G IL-18 haplotype is associated with a higher incidence of postprophylaxis CMV replication. The prior identification of this polymorphism could help select alternative measures to prevent delayed-onset CMV infection in these patients.