title: The role of single nucleotide polymorphisms, contained in proinflammatory cytokine genes, in the development of congenital infection with human cytomegalovirus in fetuses and neonates.
abstract: OBJECTIVE
  The research project targeted the distribution of genotypes, alleles and haplotypes in single nucleotide polymorphisms (SNPs) within the interleukin (IL) 1A, IL1B, IL6, IL12B and TNFA genes, in fetuses and neonates, congenitally infected with human cytomegalovirus (HCMV), and among uninfected controls.
  
  
  METHODS
  The study included 20 fetuses and neonates with congenital HCMV infection and 31 control individuals. The genotypes in SNPs of the studied cytokine genes were identified by a self-designed nested PCR-RFLP assays. Selected genotypes, representing distinct variants in analyzed polymorphisms, were confirmed by sequencing. The relationship between the genetic status of the studied polymorphisms and congenital infection development was estimated, using a logistic regression model.
  
  
  RESULTS
  The CT haplotype, composed of C allele determined in IL1A -889 C > T and T allele in IL1B +3954 C > T SNP, increased the risk of congenital HCMV infection, as well as the onset of disease related symptoms (P ≤ 0.0001). Considering disease outcome, the risk of development of symptoms, was increased among the CT heterozygotes in IL1A -889 C > T polymorphism (OR 2.86, 95% CI 0.24-33.90; P = 0.045). Moreover, multiple-SNP variants CCGAG in the range of all the SNPs, analyzed in the study, increased the risk of congenital infection with HCMV (OR 7.94, 95% CI 1.38-45.69; P = 0.026).
  
  
  CONCLUSIONS
  Polymorphisms within the proinflammatory cytokine genes may contribute to the development of congenital infection with HCMV.
authors.affiliation: Scientific Laboratory of the Center of Medical Laboratory Diagnostics and Screening, Polish Mother's Memorial Hospital - Research Institute, Lodz, Poland; Department of Perinatology and Gynecology, Polish Mother's Memorial Hospital - Research Institute, Lodz, Poland. Electronic address: wwujcicka@yahoo.com.
authors.forename: Wioletta
authors.initials: W
authors.lastname: Wujcicka
authors.affiliation: 2nd Chair of Obstetrics and Gynecology, Duchess Anna Mazowiecka Public Teaching Hospital, Warsaw, Poland. Electronic address: janszczesnywilczynski@gmail.com.
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. Electronic address: eparadowska@cbm.pan.pl.
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. Electronic address: mstudzinska@cbm.pan.pl.
authors.forename: Mirosława
authors.initials: M
authors.lastname: Studzińska
authors.affiliation: Department of Perinatology and Gynecology, Polish Mother's Memorial Hospital - Research Institute, Lodz, Poland. Electronic address: dnowakowska@yahoo.com.
authors.forename: Dorota
authors.initials: D
authors.lastname: Nowakowska
mesh_terms: D016207:Cytokines / Q000235:genetics*; D003586:Cytomegalovirus Infections / Q000151:congenital* / Q000473:pathology*; D005333:Fetus; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006801:Humans; D007231:Infant, Newborn; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA
chemical_list: D016207:Cytokines
keywords: Congenital infection; Genetic predisposition; Human cytomegalovirus (HCMV); IL12B; IL1B; IL6; Interleukin (IL) 1A; Proinflammatory cytokines; Single nucleotide polymorphisms (SNPs); TNF