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

Journal of Perinatology volume 33, pages 341–346 (2013)Cite this article

Subjects

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).

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.

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Acknowledgements

We would like to acknowledge the help and support of Sharon Nelson (NNP at Waukesha Memorial Hospital), research nurses (Kathleen Meskin and Laura Lane) at Children’s Hospital of Wisconsin and the NICU and labor and delivery staff in recruiting patients. Last but not the least, we would like to thank all the parents and their infants who agreed to participate in the study.

Project support: This study was partly supported by pilot grants from the Children’s Research Institute and NIEHS Children’s Environmental Health Sciences Core (ES004184) Center to V.S.

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Authors and Affiliations

  1. Pediatrics, Medical College of Wisconsin and Children’s Research Institute, Children’s Hospital and Health Systems, Milwaukee, WI, USA

    V R Karody, M Le, K Meskin, S Klemm, P Simpson, R Hines & V Sampath

  2. Neonatology, Waukesha Memorial Hospital, Waukesha, WI, USA

    S Nelson

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  1. V R Karody
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Correspondence to V R Karody.

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Karody, V., Le, M., Nelson, S. et al. A TIR domain receptor–associated protein (TIRAP) variant SNP (rs8177374) confers protection against premature birth. J Perinatol 33, 341–346 (2013). https://doi.org/10.1038/jp.2012.120

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