Toll-like receptor genetic variants are associated with Gram-negative infections in VLBW infants

J Perinatol. 2013 Oct;33(10):772-7. doi: 10.1038/jp.2013.80. Epub 2013 Jul 18.

Abstract

Objective: To test the hypothesis that single-nucleotide polymorphisms (SNPs) in Toll-like receptor (TLR) genes alter susceptibility to bacterial infections and modulate white blood cell (WBC) counts during infections in very low birth weight (VLBW) infants (birth weight <1500 g).

Study design: VLBW infants recruited in a multicenter study were genotyped for nine functional TLR SNPs and associations between SNPs and infection rates examined. WBC counts obtained during infections were compared among infants with and without SNPs.

Result: In our cohort (n=408), 90 infants developed bacterial infections. Presence of TLR4 (rs4986790 and rs4986791) variants were associated with Gram-negative (G-ve) infections. Female infants heterozygous for the X-linked IRAK1 (rs1059703) SNP had less G-ve infections. In regression models controlling for confounders, the TLR4 (rs4986790) SNP was associated with increased G-ve infections. The TLR5 (rs5744105) variant was associated with elevated WBC counts during infections.

Conclusion: TLR genetic variants can contribute to increased risk of bacterial infections and altered immune responses in VLBW infants.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Black or African American / genetics
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genetic Variation
  • Gram-Negative Bacterial Infections / blood
  • Gram-Negative Bacterial Infections / genetics*
  • Humans
  • Immunity, Innate / genetics
  • Infant, Newborn
  • Infant, Premature
  • Infant, Premature, Diseases / genetics*
  • Infant, Very Low Birth Weight / physiology*
  • Interleukin-1 Receptor-Associated Kinases / genetics
  • Leukocyte Count
  • Logistic Models
  • Male
  • Polymorphism, Single Nucleotide / genetics*
  • Risk Factors
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 5 / genetics
  • Toll-Like Receptors / genetics*
  • White People / genetics

Substances

  • Toll-Like Receptor 4
  • Toll-Like Receptor 5
  • Toll-Like Receptors
  • IRAK1 protein, human
  • Interleukin-1 Receptor-Associated Kinases