Influence of Single-nucleotide Polymorphisms in (rs3775291) and (rs352139) on the Risk of CMV Infection in Kidney Transplant Recipients

Risk stratification for cytomegalovirus (CMV) infection after kidney transplantation (KT) remains to be determined. Since endosomal toll-like receptors (TLRs) are involved in viral sensing, we investigated the impact of common single-nucleotide polymorphisms (SNPs) located within and genes on the occurrence of overall and high-level (≥1,000 IU/ml) CMV infection in a cohort of 197 KT recipients. Homozygous carriers of the minor allele of (rs3775291) had higher infection-free survival compared with reference allele carriers (60.0% for TT versus 42.3% for CC/CT genotypes; -value = 0.050). Decreased infection-free survival was observed with the minor allele of (rs352139) (38.2% for TC/CC versus 59.3% for TT genotypes; -value = 0.004). After multivariable adjustment, the recessive protective effect of the (rs3775291) TT genotype was confirmed (adjusted hazard ratio [aHR]: 0.327; 95% CI: 0.167-0.642; -value = 0.001), as was the dominant risk-conferring effect of (rs352139) TC/CC genotypes (aHR: 1.865; 95% CI: 1.170-2.972; -value = 0.009). Carriers of the (rs352139) TC/CC genotypes showed lower CMV-specific interferon-γ-producing CD4+ T-cell counts measured by intracellular cytokine staining compared with the TT genotype (median of 0.2 versus 0.7 cells/μl; -value = 0.003). In conclusion, genotyping may inform CMV infection risk after KT.