Genetic polymorphisms in TLR3, IL10 and CD209 influence the risk of BK polyomavirus infection after kidney transplantation

Abstract

Genetic determinants of BK polyomavirus infection after kidney transplantation remain poorly investigated. We assessed the potential impact of 13 different single nucleotide polymorphisms within genes mainly involved in innate immune responses on the risk of BKPyV viremia in 204 KT recipients. After a median follow-up of 1121.5 days, the cumulative incidence of any-level BKPyV viremia was 24.5% (50/204). There was a significant association between the minor T allele of TLR3 (rs3775291) SNP and the development of BKPyV viremia (adjusted hazard ratio [aHR]: 2.16; 95% confidence interval [CI]: 1.08-4.30; P value = 0.029), whereas the minor G allele of CD209 (rs4804803) SNP exerted a protective role (aHR: 0.54; 95% CI: 0.29-1.00; P value = 0.050). A higher incidence of BKPyV viremia was also observed for the minor G allele of IL10 (rs1800872) SNP, although the absence of BKPyV events among homozygotes for the reference allele prevented multivariable analysis. The BKPyV viremia-free survival rate decreased with the increasing number of unfavorable genotypes (100% [no unfavorable genotypes], 85.4% [1 genotype], 70.9% [2 genotypes], 52.5% [3 genotypes]; P value = 0.008). In conclusion, SNPs in TLR3, CD209 and IL10 genes play a role in modulating the susceptibility to any-level BKPyV viremia among KT recipients.

Figure 1

Comparison of Kaplan–Meier BKPyV viremia-free survival curves according to the genotype of selected SNPs (a) carriers of the TT genotype of IL10 (rs1800872) (blue line) were compared to patients with TG/GG genotypes (red line) (log-rank P value = 0.015); (b) carriers of CC/CT genotypes of TLR3 (rs3775291) (blue line) were compared to TT genotype carriers (red line) (log-rank P value = 0.026); and (c) carriers of the AA genotype of CD209 (rs4804803) (blue line) were compared to those with AG/GG genotypes (red line) (log-rank P value = 0.096). BKPyV: BK polyomavirus; SNP: single-nucleotide polymorphism.

Figure 2

Comparison of Kaplan–Meier BKPyV viremia-free survival curves according to the number of unfavorable genotypes in selected SNPs: 0 (green line), 1 (blue line), 2 (orange line) and 3 unfavorable genotypes (red line) (log-rank P value = 0.008). Unfavorable genotypes were categorized as follow: TG/GG for IL10 (rs1800872), TT for TLR3 (rs3775291), and AA for CD209 (rs4804803). BKPyV: BK polyomavirus.