title: Single nucleotide polymorphism in toll-like receptor 6 is associated with a decreased risk for ureaplasma respiratory tract colonization and bronchopulmonary dysplasia in preterm infants.
abstract: BACKGROUND
  Ureaplasma spp. respiratory tract colonization is a risk factor for bronchopulmonary dysplasia (BPD) in preterm infants, but differences in host susceptibility have not been elucidated. We hypothesized that variants in genes regulating the innate immune response are associated with altered risk for Ureaplasma spp. respiratory colonization and BPD in preterm infants.
  
  
  METHODS
  Twenty-four tag single nucleotide polymorphisms (SNPs) from Toll-like receptor (TLR)1, TLR2, TLR4 and TLR6 were assayed in 298 infants <33 weeks gestation who had serial respiratory cultures for Ureaplasma spp. and were evaluated for BPD.
  
  
  RESULTS
  The majority of subjects (N = 205 [70%]) were African-American. One hundred ten (37%) were Ureaplasma positive. Four SNPs in TLR2 and TLR6 were significantly associated with Ureaplasma respiratory tract colonization. Single SNPs in TLR2, TLR4 and TLR6 were associated with BPD. TLR6 SNP rs5743827 was associated with both a decreased risk for Ureaplasma respiratory tract colonization and decreased risk for BPD (odds ratio: 0.54 [0.34-0.86] and odds ratio: 0.54 [0.31-0.95], respectively). There was a significant additive interaction between Ureaplasma colonization and genotype at TLR6 SNP rs5743827 (Padditive = 0.023), with an attributable proportion due to interaction of 0.542.
  
  
  CONCLUSIONS
  Polymorphisms in host defense genes may alter susceptibility to Ureaplasma infection and severity of the inflammatory response contributing to BPD. These observations implicate host genetic susceptibility as a major factor in BPD pathogenesis in Ureaplasma-infected preterms.
authors.affiliation: Department of Medicine, University of Maryland, Baltimore School of Medicine, Baltimore, MD, USA.
authors.forename: Alexandra H
authors.initials: AH
authors.lastname: Winters
authors.forename: Tricia D
authors.initials: TD
authors.lastname: Levan
authors.forename: Stefanie N
authors.initials: SN
authors.lastname: Vogel
authors.forename: Kirsty L
authors.initials: KL
authors.lastname: Chesko
authors.forename: Toni I
authors.initials: TI
authors.lastname: Pollin
authors.forename: Rose M
authors.initials: RM
authors.lastname: Viscardi
mesh_terms: D001997:Bronchopulmonary Dysplasia / Q000235:genetics* / Q000382:microbiology; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012141:Respiratory Tract Infections / Q000235:genetics* / Q000382:microbiology; D051216:Toll-Like Receptor 6 / Q000235:genetics*; D014509:Ureaplasma / Q000302:isolation & purification; D016869:Ureaplasma Infections / Q000235:genetics* / Q000382:microbiology
chemical_list: C495368:TLR6 protein, human; D051216:Toll-Like Receptor 6