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Background  Some single nucleotide polymorphisms (SNP), located in  Toll-like receptor  ( TLR ) genes, were reported to be associated with human cytomegalovirus (HCMV) infections. The study was aimed to assess the correlation of SNPs at  TLR4  and  TLR9  genes with the occurrence of congenital cytomegaly, based on available samples.    Methods  Reported case-control study included both HCMV infected and non-infected fetuses and newborns. The specimens were classified to the molecular analyses, based on serological features of the recent infection and HCMV DNAemia in body fluids.  TLR  SNPs were studied, using multiplex nested PCR-RFLP assay, and determined genotypes were confirmed by sequencing. Hardy-Weinberg equilibrium was assessed for the identified genotypes. The linkage disequilibrium was also estimated for  TLR4  SNPs. A relationship between the status of  TLR  genotypes and congenital cytomegaly development was estimated, using a logistic regression model.    Results  Hardy Weinberg equilibrium was observed for almost all SNPs, both infected and non-infected patients, with exception of  TLR4  896 A>G polymorphism in the control group (P≤0.050).  TLR4  896 A>G and 1196 C>T SNPs were found in linkage disequilibrium in both study groups (P≤0.050). The CC genotype at  TLR4  1196 SNP and the GA variant at  TLR9  2848 G>A SNP were significantly associated with HCMV infection (P≤0.050). The risk of congenital cytomegaly was higher in heterozygotes at  TLR9  SNP than in the carriers of other genotypic variants at the reported locus (OR 4.81; P≤0.050). The GC haplotype at  TLR4  SNPs and GCA variants at  TLR4  and  TLR9  SNPs were significantly associated with HCMV infection (P≤0.0001). The ACA variants were more frequent among fetuses and neonates with symptomatic, rather than asymptomatic cytomegaly (P≤0.0001).    Conclusions    TLR4  and  TLR9  polymorphisms may contribute to the development of congenital infection with HCMV in fetuses and neonates. The  TLR9  2848 GA heterozygotic status possibly predisposes to HCMV infection, increasing the risk of congenital cytomegaly development.

TLR9 2848 GA Heterozygotic Status Possibly Predisposes Fetuses and Newborns to Congenital Infection with Human Cytomegalovirus