title: A TIR domain receptor-associated protein (TIRAP) variant SNP (rs8177374) confers protection against premature birth.
abstract: OBJECTIVE
  To investigate whether single nucleotide polymorphisms (SNPs) in genes encoding the Toll-like receptor (TLR) signaling pathway modulate susceptibility to preterm birth (PTB).
  
  
  METHODS
  Prospective case-control study examining the contribution of nine TLR SNPs to PTB (<37 weeks) and PTB <32 weeks. Genotyping was done on neonatal blood using a multiplexed single-base extension assay. Chi-square test, Fischer's exact test and classification trees were used for data analysis.
  
  
  RESULTS
  Preterm infants (n=177) were more likely to be African American (P=0.02), and were more likely to be born to mothers who smoked (P=0.007), had pregnancy-induced hypertension (PIH; P=0.002) and placental abruption (P=0.0004) when compared with term infants (n=146). The TLR2, TLR4, TLR5, TLR9, nuclear factor-kappa B1 (NFκB1), NFκBIA and IRAK1 variants were not associated with PTB whereas the TIR domain receptor-associated protein (TIRAP) variant was more prevalent in term infants when compared with preterm infants born <32 weeks (P=0.004). PTB <32 weeks was more prevalent in infants without the TIRAP variant whose mothers had PIH and did not smoke (P=0.001). Presence of the TIRAP variant protected against PTB <32 weeks (P=0.015) in Caucasian infants.
  
  
  CONCLUSIONS
  In our study, a TLR pathway adapter variant (TIRAP (rs8177374)) protected against PTB<32 weeks, supporting our hypothesis that genetic variation in the innate immune signaling pathway contributes to altered risk of PTB.
authors.affiliation: Pediatrics, Medical College of Wisconsin and Children's Research Institute, Children's Hospital and Health Systems, Milwaukee, WI, USA. vkarody@mcw.edu
authors.forename: V R
authors.initials: VR
authors.lastname: Karody
authors.forename: M
authors.initials: M
authors.lastname: Le
authors.forename: S
authors.initials: S
authors.lastname: Nelson
authors.forename: K
authors.initials: K
authors.lastname: Meskin
authors.forename: S
authors.initials: S
authors.lastname: Klemm
authors.forename: P
authors.initials: P
authors.lastname: Simpson
authors.forename: R
authors.initials: R
authors.lastname: Hines
authors.forename: V
authors.initials: V
authors.lastname: Sampath
mesh_terms: D001741:Black or African American / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D047928:Premature Birth / Q000235:genetics*; D017472:Receptors, Interleukin-1 / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D051193:Toll-Like Receptors / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D008562:Membrane Glycoproteins; D017472:Receptors, Interleukin-1; C434984:TIRAP protein, human; D051193:Toll-Like Receptors