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A TIR domain receptor-associated protein (TIRAP) variant SNP (rs8177374) confers protection against premature birth.
MedLine Citation:
PMID:  23047423     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Objective:To investigate whether single nucleotide polymorphisms (SNPs) in genes encoding the Toll-like receptor (TLR) signaling pathway modulate susceptibility to preterm birth (PTB).Study Design: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.Result: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.Conclusion: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.Journal of Perinatology advance online publication, 4 October 2012; doi:10.1038/jp.2012.120.
Authors:
V R Karody; M Le; S Nelson; K Meskin; S Klemm; P Simpson; R Hines; V Sampath
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-04
Journal Detail:
Title:  Journal of perinatology : official journal of the California Perinatal Association     Volume:  -     ISSN:  1476-5543     ISO Abbreviation:  J Perinatol     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8501884     Medline TA:  J Perinatol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Pediatrics, Medical College of Wisconsin and Children's Research Institute, Children's Hospital and Health Systems, Milwaukee, WI, USA.
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