A TIR domain receptor-associated protein (TIRAP) variant SNP (rs8177374) confers protection against premature birth

作者：Karody V R^*; Le M; Nelson S; Meskin K; Klemm S; Simpson P; Hines R; Sampath V

来源：Journal of Perinatology, 2013, 33(5): 341-346.

DOI：10.1038/jp.2012.120

• TIR domain receptor-associated protein (TIRAP)
• single nucleotide polymorphism
• preterm birth
• Toll-like receptor
• pregnancy-induced hypertension

OBJECTIVE: To investigate whether single nucleotide polymorphisms (SNPs) in genes encoding the Toll-like receptor (TLR) signaling pathway modulate susceptibility to preterm birth (PTB). %26lt;br%26gt;STUDY DESIGN: Prospective case-control study examining the contribution of nine TLR SNPs to PTB (%26lt;37 weeks) and PTB %26lt;32 weeks. Genotyping was done on neonatal blood using a multiplexed single-base extension assay. Chi-square test, Fischer%26apos;s exact test and classification trees were used for data analysis. %26lt;br%26gt;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 (NF kappa B1), NF kappa BIA 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 %26lt;32 weeks (P = 0.004). PTB %26lt;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 %26lt;32 weeks (P = 0.015) in Caucasian infants. %26lt;br%26gt;CONCLUSION: In our study, a TLR pathway adapter variant (TIRAP (rs8177374)) protected against PTB%26lt;32 weeks, supporting our hypothesis that genetic variation in the innate immune signaling pathway contributes to altered risk of PTB. Journal of Perinatology (2013) 33, 341-346; doi:10.1038/jp.2012.120; published online 4 October 2012

• 出版日期2013-5