P0078INVESTIGATION THE VARIANTS AT THE BINDING SITE OF INFLAMMATORY TRANSCRIPTION FACTOR IN PATIENTS WITH ESRD

Abstract

Abstract Background and Aims Inflammation is an important factor for enhancing the disease process from chronic kidney disease (CKD) to end-stage renal disease (ESRD). Nuclear factor-kappa B (NF-κB) is a transcription factor that regulates the expression of genes involved in inflammation. We investigated the potential association with the gene polymorphism of transcription factor binding site of NF-κB in ESRD patients. Method We used the Taiwan Biobank database, University of California, Santa Cruz, reference genome, chromatin immunoprecipitation sequencing database to find the SNPs at potential binding sites of NF-κB. In addition, we performed a case–control study and genotyped 847 patients with ESRD and 846 healthy controls at Tri-Service-General-Hospital from 2015 to 2016. Further we used ChIP-assay and Luciferase reporter assay to identify the binding activity at different genotype. Results Results of biometrics screening in the databases revealed 15 SNPs with the potential binding site of NF-κB. Genotype distributions of rs9395890 were significantly different in ESRD cases and healthy controls (P = 0.032). In the Dominant model, rs9395890 with T allele had a higher risk of ESRD (P = 0.032; odds ratio [OR] = 1.32, 95% confidence interval [CI] = 0.99–1.76). The ChIP assay reveals that around 1.49 times enrichment of NF-κB of the variant type TT when compared to that of the wild type GG in the rs9395890 (P<0.027; TT=3.20±0.16, GT=2.81±0.20, GG=1.71±0.18,) and the luciferase activity curve showed T allele was higher than G allele. Conclusion In conclusion, we demonstrate that rs9395890 may be associated with ESRD in the Taiwanese population.