Impact of Inhibitor kappa B-alpha (IkB-α) Promoter Polymorphisms On the Risk of Cytomegalovirus Infection Among Hispanic Renal Transplant Recipients.

Abstract

Background: Cytomegalovirus (CMV) is one of the most common cause of viral infection, causing morbidity and mortality among kidney transplant recipients (RTRs). The dimeric NF-kB transcription factors play critical roles in diverse cellular processes including adaptive and innate immunity, cell differentiation, proliferation and apoptosis. It regulates the expression of numerous genes that play a key role in the inflammatory and immune responses. Inhibitors of NF-kB, known as inhibitor kappa B-alpha (IkB-α), block NF-kB transcriptional activity by forming stable IkB-α:NF-kB complexes. The aim was to investigate the association of gene polymorphisms in the NF-kB and IkB pathway with CMV infection in RTRs. Methods: IkB-α promoter polymorphisms at position -881 (A/G), -826 (C/T), and 297 (C/T) were studied in 247 RTRs (52 RTRs with CMV infection and 195 without CMV infection), using DNA-based polymerase chain reaction with sequence-specific primers and restriction. In the case of NF-kB genotypes, the following single nucleotide polymorphisms (SNPs) were included: NF-kB1 (rs3774959, rs3774932, rs3774937, rs230526, rs230519), NF-kB2 (rs1056890, rs7897947, rs12769316) and NF-kB inducing kinase (NIK) (rs9908330, rs7222094). Results: Median time to CMV infection was 6 months with a mean peak CMV viral load of 7925 copies per ml. Patients with donor-positive/recipient-negative [D+/R-] serostatus were found to be associated with a high risk of CMV infection (p=0.001). A statistically significant correlation was found between IkB-α -297T allele polymorphism and the risk of CMV. Three common haplotypes were found, of which haplotype 2 (GTT) was significantly associated with an increased risk for CMV infected group as compared to non-CMV group (p=0.01). The association was independently significant in multiple logistic regression (p=0.02) along with serologic status D+/R-, acute rejection and thymoglobulin induction. The allelic as well as genotypic frequencies of NF-kB SNPs did not significantly differ between CMV infection and non-CMV group. Conclusion: These results indicated that the NF-kB activation pathway might be associated with the CMV infection.