title: TLR9 2848 GA heterozygotic status possibly predisposes fetuses and newborns to congenital infection with human cytomegalovirus.
abstract: 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.
authors.affiliation: Scientific Laboratory of Center of Medical Laboratory Diagnostics, Polish Mother's Memorial Hospital-Research Institute, Lodz, Poland.
authors.forename: Wioletta
authors.initials: W
authors.lastname: Wujcicka
authors.affiliation: Laboratory of Molecular Virology and Biological Chemistry, Institute of Medical Biology, Polish Academy of Sciences, Lodz, Poland.
authors.forename: Edyta
authors.initials: E
authors.lastname: Paradowska
authors.affiliation: Laboratory of Molecular Virology and Biological Chemistry, Institute of Medical Biology, Polish Academy of Sciences, Lodz, Poland.
authors.forename: Mirosława
authors.initials: M
authors.lastname: Studzińska
authors.affiliation: Scientific Laboratory of Center of Medical Laboratory Diagnostics, Polish Mother's Memorial Hospital-Research Institute, Lodz, Poland.
authors.forename: Zuzanna
authors.initials: Z
authors.lastname: Gaj
authors.affiliation: Department of Perinatology and Gynecology, Polish Mother's Memorial Hospital-Research Institute, Lodz, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Wilczyński
authors.affiliation: Laboratory of Molecular Virology and Biological Chemistry, Institute of Medical Biology, Polish Academy of Sciences, Lodz, Poland.
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Leśnikowski
authors.affiliation: Department of Perinatology and Gynecology, Polish Mother's Memorial Hospital-Research Institute, Lodz, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Nowakowska
mesh_terms: D016022:Case-Control Studies; D003586:Cytomegalovirus Infections / Q000151:congenital* / Q000235:genetics*; D005333:Fetus / Q000002:abnormalities / Q000821:virology; D020022:Genetic Predisposition to Disease; D006801:Humans; D007231:Infant, Newborn; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D051217:Toll-Like Receptor 9 / Q000235:genetics*
chemical_list: C495345:TLR4 protein, human; C495371:TLR9 protein, human; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9
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