NR1I2 8055 Gene Polymorphism of Pregnane X Nuclear Receptor Is Not a Risk Factor for Polyomavirus BK (BKV) Infection in HLA-Sensitized (HS) Patients Transplanted After Desensitization With IVIG and Rituximab.

Abstract

Background: We previously reported a higher rate of BKV infection in HS patients transplanted after desensitization with IVIG+rituximab. Desensitization, likely rituximab, was found to be a significant risk factor for BKV infection. A recent study reported a significant association of the NR1I2 8055T allele of pregnane X nuclear receptor promoting the clearance of drugs with higher dose-adjusted tacrolimus exposure, resulting in over-immunosuppression and higher BK viremia rate in 8055T carriers compared to wild type (8055CC) individuals. Here we examine if the 8055T allele contributes to higher BKV infection rate in our HS transplant patients. Methods: Archived DNA samples from 211 HS kidney transplant patients were submitted for SNP genotyping assay to determine NR1I2 8055 genotypes (CC, CT and TT). BKV infection rate was compared among the genotypes. Real time-BKV-PCR>250 copies/ml plasma was considered positive.Results: Overall, 33/211 (16%) patients developed BK viremia. (Table 1). There was no significant difference in BK viremia rates and peak viral copies between wild-type (CC) vs. T allele carriers (CT and TT). No patient with TT genotype developed BK viremia, while 17% in C allele carriers did so (p<0.05). A similar result was obtained when BK viremia >2.5x103copies/ml plasma, a level of viremia that typically requires treatment, was used for the analysis (BKV+: 9/107 [8%] in CC vs 11/104 [11%] in CT + TT, NS; 20/190 [10.5%] in CC + CT vs. 0/21 [0%] in TT, p=0.23).Conclusions: NR1I2 8055 polymorphism does not contribute to high rate of BKV infection and is not a risk factor for BKV infection in our HS kidney transplant patients who were desensitized with IVIG and rituximab followed by transplantation. It is possible that other risk factors, such as desensitization, for BK viremia in this population diminish the influence of the NR1I2 8055 polymorphism.Table: No Caption available.