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

Journal of Perinatology volume 33, pages 772–777 (2013)Cite this article

Subjects

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.

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Acknowledgements

We acknowledge the contribution of research nurses Kathleen Meskin and Laura Lane for their help with recruitment of study infants. This study was partly supported by the NIEHS Children’s Environmental Health Sciences Core (ES004184) Center pilot and 8KL2TR000056 grants to V Sampath.

Author information

Authors and Affiliations

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

    V Sampath, J He, P M Simpson & R N Hines

  2. Children’s Hospitals and Clinics of Minnesota, Minneapolis, MN, USA

    N P Mulrooney

  3. Department of Pediatrics, Wheaton Franciscan Health Care, Milwaukee, WI, USA

    J S Garland

  4. Department of Pediatrics, Rush University Medical Center, Chicago, IL, USA

    A L Patel

  5. Neonatal Intensive Care Experts, Louisville, KY, USA

    J D Cohen

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  1. V Sampath
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  2. N P Mulrooney
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  4. J He
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  5. A L Patel
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  7. P M Simpson
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Correspondence to V Sampath.

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Supplementary Information accompanies the paper on the Journal of Perinatology website

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Sampath, V., Mulrooney, N., Garland, J. et al. Toll-like receptor genetic variants are associated with Gram-negative infections in VLBW infants. J Perinatol 33, 772–777 (2013). https://doi.org/10.1038/jp.2013.80

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