Association between individual and combined SNPs in genes related to innate immunity and incidence of CMV infection in seropositive kidney transplant recipients
Fernández-Ruiz M1, Corrales I, Arias M, Campistol JM, Giménez E, Crespo J, López-Oliva MO, Beneyto I, Martín-Moreno PL [SP], Llamas-Fuente F, Gutiérrez A, García-Álvarez T, Guerra-Rodríguez R, Calvo N, Fernández-Rodríguez A, Tabernero-Romo JM, Navarro MD, Ramos-Verde A, Aguado JM, Navarro D; OPERA Study Group.
(1) Unit of Infectious Diseases, Hospital Universitario 12 de Octubre, Instituto de Investigación Hospital 12 de Octubre, Madrid, Spain.
Magazine: The American Society of Transplantation and the American Society of Transplant Surgeons
Date: May 15, 2015Nephrology [SP]
In this study, we assessed the association between single-nucleotide polymorphisms (SNPs) in seven candidate genes involved in orchestrating the immune response against cytomegalovirus (CMV) and the 12-month incidence of CMV infection in 315 CMV-seropositive kidney transplant (KT) recipients.
Patients were managed either by antiviral prophylaxis or preemptive therapy. CMV infection occurred in 140 patients (44.4%), including 13 episodes of disease. After adjusting for various clinical covariates, patients harboring T-allele genotypes of interleukin-28B (IL28B) (rs12979860) SNP had lower incidence of CMV infection (adjusted hazard ratio [aHR]: 0.66; 95% confidence interval [CI]: 0.46-0.96; p-value = 0.029). In the analysis restricted to patients not receiving prophylaxis, carriers of the TT genotype of toll-like receptor 9 (TLR9) (rs5743836) SNP had lower incidence of infection (aHR: 0.61; 95% CI: 0.38-0.96; p-value = 0.035), whereas the GG genotype of dendritic cell-specific ICAM 3-grabbing nonintegrin (DC-SIGN) (rs735240) SNP exerted the opposite effect (aHR: 1.86; 95% CI: 1.18-2.94; p-value = 0.008).
An independent association was found between the number of unfavorable SNP genotypes carried by the patient and the incidence of CMV infection.
In conclusion, specific SNPs in IL28B, TLR9 and DC-SIGN genes may play a role in modulating the susceptibility to CMV infection in CMV-seropositive KT recipients.
CITATION Am J Transplant. 2015 May;15(5):1323-35. doi: 10.1111/ajt.13107. Epub 2015 Mar 16.
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