A toll-like receptor 9 (rs352140) variant is associated with placental inflammation in newborn infants

Abstract

Objective: Chorioamnionitis contributes to premature birth and associated postnatal morbidity. The genetic basis of altered immune responses underlying placental inflammation (PI) remains understudied. The aim of this study was to evaluate the relationship among TLR signaling pathway polymorphisms and different patterns of PI.

Methods: Prospective cohort study in infants involving cord blood collection and placental examination for PI. One hundred and fifty-nine infants enrolled in study out of which 28 were term (eight with PI) and 131 preterm (47 with PI). DNA from blood was genotyped for SNPs in TLR2, 4, 5, 9, NFKBI, NFKBIA, TIRAP, and IRAK1 genes using multiplexed single base extension assay.

Results: While there were no differences in BW, GA, gender, race, and SPL among infants with or without PI, there was a higher incidence of PPROM, maternal smoking, drug use, and clinical chorioamnionitis among infants with PI. Out of nine TLR variants, only CT and/or TT genotypes of the TLR9 variant (rs352140) were significantly associated (p = 0.004) with any PI and maternal pattern of inflammation (p = 0.012) both by univariate analysis and logistic regression.

Conclusions: The presence of a variant T allele in a common SNP (rs352140) in the TLR9 gene whose product recognizes bacterial DNA is associated with increased PI.

• Chorioamnionitis
• innate immunity
• placental inflammation
• toll-like receptor 9 polymorphisms
• rs352140

Acknowledgements

The authors would also like to acknowledge the help and support of our research nurses (Kathleen Meskin and Laura Lane) at Children’s Hospital of Wisconsin and the NICU and labor and delivery staff in recruiting patients. A special mention should also go to all the parents and their infants, who agreed to participate in the study, without whom this endeavor would not have been possible.

Declaration of interest

The authors report no declarations of interest. The study was partly supported by Children’s Research Institute and 8KL2TR000056 Grants to Venkatesh Sampath.