Background: BK virus nephropathy (BKVN) is a common viral infection that affects up to 10% of renal transplant recipients (RTRs), causing allograft dysfunction and graft loss. Nuclear factor of activated T cells (NFAT) is known to have an important regulatory role in BK virus infection and viral transcription. The aim of this study was to assess whether the NFATc4 gene polymorphisms correlate with the risk of BKVN.
Methods: We retrospectively reviewed a total of 237 RTRs from 756 RTRs who had received kidney allografts at St. Vincent Medical Center between 1/2004 and 10/2011. Among 756 RTRs, a total of 62 patients were diagnosed with BKVN. The 175 patients without BKVN were genotyped as a control group. All patients presented with acute elevation in serum creatinine and were diagnosed with BKVN after renal allograft biopsy with further confirmation by PCR assay for BK viral DNA in plasma. We genotyped five single nucleotide polymorphisms (SNPs) (rs1955915, rs10141896, rs2243891, rs2295298, rs2229233) spanning the entire NFATc4 gene. Stepwise logistic regression analysis was used to generate univariate and multivariate odd ratios to validate the significance of trends.
Results: Sixty-two patients were diagnosed with BKVN for an incidence of 9.4 %. Cumulative incidence was 3.3% and 6.0% in 6 months and 1 year, respectively. NFATc4 (rs1955915) CC genotype was statistically significant associated with susceptibility to BKVN (OR: 2.57, 95% CI: 1.28-5.17, p=0.006) while the T allele (TT + CT) genotype appeared to be a marker for protection against BKVN (OR: 0.38, 95% CI: 0.19-0.78, p=0.007). The analysis of NFATc4 haplotypes showed that the C-G-G-T-C, haplotype was associated with a significantly reduced risk for BKVN (OR: 0.49, 95% CI: 0.31-0.76, p=0.001) while T-G-G-T-C haplotype was associated with a higher risk for BKVN. Of the nongenetic risk factors, use of tacrolimus, advanced age (≥45 years) and male recipients were associated with increased risk for BKVN. Four other SNPs did not show any significant association between BKVN and control groups.
Conclusion: The NF-ATc4 gene is expressed in lymphocytes. Polymorphisms in the NFATc4 gene may confer certain protection or predisposition for BKVN.
To cite this abstract in AMA style:Vu D, Shah T, Qazi Y, Naraghi R, Kawewat B, Hutchinson I, Min D. Polymorphisms in the Transcription Factor NFATc4 Gene Are Associated with BKVN in Renal Allograft Recipients [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/polymorphisms-in-the-transcription-factor-nfatc4-gene-are-associated-with-bkvn-in-renal-allograft-recipients/. Accessed October 27, 2020.
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