Impact of NF-κB gene polymorphism on allograft outcome in Hispanic renal transplant recipients

BackgroundThe dimeric NF-κB 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 response during kidney allograft rejection. This study aims to determine the association of NF-κB gene polymorphisms with allograft outcomes in the Hispanic renal transplant recipients.MethodsA total of 607 Hispanic renal transplant recipients at St. Vincent Medical Center between 2001 and 2010 were included in this study. The NF-κB genotypes were studied along with clinical data. In the case of NF-κB genotypes, the following single nucleotide polymorphisms (SNPs) were included: NF-κB1 (rs3774959, rs3774932, rs3774937, rs230526, rs230519), NF-κB2 (rs1056890, rs7897947, rs12769316) and NF-κB inducing kinase (NIK) (rs9908330, rs7222094). The association of each genotype with renal allograft survival and acute rejection was evaluated.ResultsNF-κB1 (rs3774937) CC genotype showed protective association with allograft rejection (OR = 0.66, 95% CI = 0.44–0.99, p = 0.04). There was a significant increase in allograft survival time associated with the NF-κB1 (rs3774959) A allele (OR = 0.76, 95% CI = 0.60–0.98, p = 0.03) while GG genotype was associated with a higher risk of graft failure (OR = 1.51, 95% CI = 1.02–2.21, p = 0.03). There were no associations between polymorphic markers in NF-κB2 and NIK genes with allograft survival or acute rejection. Among non-genetic factors, we found that the use of tacrolimus, a deceased donor, delayed graft function and acute rejection were associated with allograft failure.ConclusionThe result of present study suggests that NF-κB1 gene polymorphisms may determine the incidence of acute rejection or graft survival among Hispanic allograft recipients.

► First associated study of NF-κB gene polymorphism with kidney allograft outcomes ► NF-kB1 (rs3774937) CC showed protective association with allograft rejection. ► NF-kB1 (rs3774959) A allele was significantly associated with graft survival. ► The GG genotype was associated with a 1.63 fold increased risk for allograft loss. ► There were no associations between NF-κB2 and NIK genes with allograft outcomes.