Association of functional genetic variants of transcription factor Forkhead Box P3 and Nuclear Factor-κB with end-stage renal disease and renal allograft outcome

Gene
Maneesh Kumar MisraSuraksha Agrawal

Abstract

The transcription factor FOXP3 and NF-κB regulates the expression of various genes that play an important role in the regulation of renal inflammation. We investigated the association of FOXP3 (rs2232365, rs3761548, rs5902434 and rs2294021) and NF-κB1 (rs28362491 and rs696) gene variants in susceptibility and prognosis of end stage renal disease (ESRD) and renal allograft outcome. We genotyped four common polymorphisms of FOXP3 and two-tag SNPs of NF-κB1 genes in 350 ESRD cases and 350 controls. Single marker analysis and SNP-SNP interaction model (one to six way combinations) was used for determination of clinical outcome of ESRD and acute rejection episode (ARE). We observed significantly higher occurrence of mutant genotypes of tag-SNPs of FOXP3 namely; rs2232365 and rs3761548 along with NF-kB1 namely; rs28362491 and rs696 in ESRD and ARE cases, suggested a risk association for ESRD and ARE. Interestingly, multifactor dimension reduction analysis suggested an increased risks of nearly 6-folds for ESRD and 23-folds for ARE cases under the six factors model which consists of tag-SNPs of FOXP3 (rs2232365, rs3761548, rs5902434 and rs2294021) and NF-kB1 (rs28362491 and rs696). Kaplan-Meier survival analysis showed the lowest over...Continue Reading

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