title: Association between individual and combined SNPs in genes related to innate immunity and incidence of CMV infection in seropositive kidney transplant recipients.
abstract: 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.
authors.affiliation: Unit of Infectious Diseases, Hospital Universitario 12 de Octubre, Instituto de Investigación Hospital 12 de Octubre, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Fernández-Ruiz
authors.forename: I
authors.initials: I
authors.lastname: Corrales
authors.forename: M
authors.initials: M
authors.lastname: Arias
authors.forename: J M
authors.initials: JM
authors.lastname: Campistol
authors.forename: E
authors.initials: E
authors.lastname: Giménez
authors.forename: J
authors.initials: J
authors.lastname: Crespo
authors.forename: M O
authors.initials: MO
authors.lastname: López-Oliva
authors.forename: I
authors.initials: I
authors.lastname: Beneyto
authors.forename: P L
authors.initials: PL
authors.lastname: Martín-Moreno
authors.forename: F
authors.initials: F
authors.lastname: Llamas-Fuente
authors.forename: A
authors.initials: A
authors.lastname: Gutiérrez
authors.forename: T
authors.initials: T
authors.lastname: García-Álvarez
authors.forename: R
authors.initials: R
authors.lastname: Guerra-Rodríguez
authors.forename: N
authors.initials: N
authors.lastname: Calvo
authors.forename: A
authors.initials: A
authors.lastname: Fernández-Rodríguez
authors.forename: J M
authors.initials: JM
authors.lastname: Tabernero-Romo
authors.forename: M D
authors.initials: MD
authors.lastname: Navarro
authors.forename: A
authors.initials: A
authors.lastname: Ramos-Verde
authors.forename: J M
authors.initials: JM
authors.lastname: Aguado
authors.forename: D
authors.initials: D
authors.lastname: Navarro
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D015815:Cell Adhesion Molecules / Q000235:genetics; D003586:Cytomegalovirus Infections / Q000097:blood / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D015994:Incidence; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D007676:Kidney Failure, Chronic / Q000097:blood / Q000235:genetics / Q000601:surgery*; D016030:Kidney Transplantation; D037181:Lectins, C-Type / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011956:Receptors, Cell Surface / Q000235:genetics; D066027:Transplant Recipients; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; D000095022:Interferon Lambda
chemical_list: D015815:Cell Adhesion Molecules; D007372:Interferons; D007378:Interleukins; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
keywords: clinical research / practice; immune regulation; infection and infectious agents; infectious disease; kidney disease: infectious; kidney transplantation / nephrology; molecular biology: single polynucleotide polymorphism; translational research / science; viral: Cytomegalovirus (CMV)