Single nucleotide polymorphism in toll-like receptor 6 is associated with a decreased risk for ureaplasma respiratory tract colonization and bronchopulmonary dysplasia in preterm infants

Alexandra H. Winters, Tricia D LeVan, Stefanie N. Vogel, Kirsty L. Chesko, Toni I. Pollin, Rose M. Viscardi

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

BACKGROUND: Ureaplasma spp. respiratory tract colonization is a risk factor for bronchopulmonary dysplasia (BPD) in preterm infants, but differences in host susceptibility have not been elucidated. We hypothesized that variants in genes regulating the innate immune response are associated with altered risk for Ureaplasma spp. respiratory colonization and BPD in preterm infants. METHODS: Twenty-four tag single nucleotide polymorphisms (SNPs) from Toll-like receptor (TLR)1, TLR2, TLR4 and TLR6 were assayed in 298 infants <33 weeks gestation who had serial respiratory cultures for Ureaplasma spp. and were evaluated for BPD. RESULTS: The majority of subjects (N = 205 [70%]) were African-American. One hundred ten (37%) were Ureaplasma positive. Four SNPs in TLR2 and TLR6 were significantly associated with Ureaplasma respiratory tract colonization. Single SNPs in TLR2, TLR4 and TLR6 were associated with BPD. TLR6 SNP rs5743827 was associated with both a decreased risk for Ureaplasma respiratory tract colonization and decreased risk for BPD (odds ratio: 0.54 [0.34-0.86] and odds ratio: 0.54 [0.31-0.95], respectively). There was a significant additive interaction between Ureaplasma colonization and genotype at TLR6 SNP rs5743827 (Padditive = 0.023), with an attributable proportion due to interaction of 0.542. CONCLUSIONS: Polymorphisms in host defense genes may alter susceptibility to Ureaplasma infection and severity of the inflammatory response contributing to BPD. These observations implicate host genetic susceptibility as a major factor in BPD pathogenesis in Ureaplasma-infected preterms.

Original languageEnglish (US)
Pages (from-to)898-904
Number of pages7
JournalPediatric Infectious Disease Journal
Volume32
Issue number8
DOIs
StatePublished - Aug 1 2013

Fingerprint

Toll-Like Receptor 6
Ureaplasma
Bronchopulmonary Dysplasia
Premature Infants
Respiratory System
Single Nucleotide Polymorphism
Ureaplasma Infections
Toll-Like Receptor 1
Odds Ratio
Genetic Predisposition to Disease
Innate Immunity
African Americans
Genes
Genotype

Keywords

  • Toll-like receptor 6
  • Ureaplasma parvum
  • Ureaplasma urealyticum
  • single nucleotide polymorphism

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Microbiology (medical)
  • Infectious Diseases

Cite this

Single nucleotide polymorphism in toll-like receptor 6 is associated with a decreased risk for ureaplasma respiratory tract colonization and bronchopulmonary dysplasia in preterm infants. / Winters, Alexandra H.; LeVan, Tricia D; Vogel, Stefanie N.; Chesko, Kirsty L.; Pollin, Toni I.; Viscardi, Rose M.

In: Pediatric Infectious Disease Journal, Vol. 32, No. 8, 01.08.2013, p. 898-904.

Research output: Contribution to journalArticle

@article{1b29e446169640c59907bc65b2cb5be5,
title = "Single nucleotide polymorphism in toll-like receptor 6 is associated with a decreased risk for ureaplasma respiratory tract colonization and bronchopulmonary dysplasia in preterm infants",
abstract = "BACKGROUND: Ureaplasma spp. respiratory tract colonization is a risk factor for bronchopulmonary dysplasia (BPD) in preterm infants, but differences in host susceptibility have not been elucidated. We hypothesized that variants in genes regulating the innate immune response are associated with altered risk for Ureaplasma spp. respiratory colonization and BPD in preterm infants. METHODS: Twenty-four tag single nucleotide polymorphisms (SNPs) from Toll-like receptor (TLR)1, TLR2, TLR4 and TLR6 were assayed in 298 infants <33 weeks gestation who had serial respiratory cultures for Ureaplasma spp. and were evaluated for BPD. RESULTS: The majority of subjects (N = 205 [70{\%}]) were African-American. One hundred ten (37{\%}) were Ureaplasma positive. Four SNPs in TLR2 and TLR6 were significantly associated with Ureaplasma respiratory tract colonization. Single SNPs in TLR2, TLR4 and TLR6 were associated with BPD. TLR6 SNP rs5743827 was associated with both a decreased risk for Ureaplasma respiratory tract colonization and decreased risk for BPD (odds ratio: 0.54 [0.34-0.86] and odds ratio: 0.54 [0.31-0.95], respectively). There was a significant additive interaction between Ureaplasma colonization and genotype at TLR6 SNP rs5743827 (Padditive = 0.023), with an attributable proportion due to interaction of 0.542. CONCLUSIONS: Polymorphisms in host defense genes may alter susceptibility to Ureaplasma infection and severity of the inflammatory response contributing to BPD. These observations implicate host genetic susceptibility as a major factor in BPD pathogenesis in Ureaplasma-infected preterms.",
keywords = "Toll-like receptor 6, Ureaplasma parvum, Ureaplasma urealyticum, single nucleotide polymorphism",
author = "Winters, {Alexandra H.} and LeVan, {Tricia D} and Vogel, {Stefanie N.} and Chesko, {Kirsty L.} and Pollin, {Toni I.} and Viscardi, {Rose M.}",
year = "2013",
month = "8",
day = "1",
doi = "10.1097/INF.0b013e31828fc693",
language = "English (US)",
volume = "32",
pages = "898--904",
journal = "Pediatric Infectious Disease Journal",
issn = "0891-3668",
publisher = "Lippincott Williams and Wilkins",
number = "8",

}

TY - JOUR

T1 - Single nucleotide polymorphism in toll-like receptor 6 is associated with a decreased risk for ureaplasma respiratory tract colonization and bronchopulmonary dysplasia in preterm infants

AU - Winters, Alexandra H.

AU - LeVan, Tricia D

AU - Vogel, Stefanie N.

AU - Chesko, Kirsty L.

AU - Pollin, Toni I.

AU - Viscardi, Rose M.

PY - 2013/8/1

Y1 - 2013/8/1

N2 - BACKGROUND: Ureaplasma spp. respiratory tract colonization is a risk factor for bronchopulmonary dysplasia (BPD) in preterm infants, but differences in host susceptibility have not been elucidated. We hypothesized that variants in genes regulating the innate immune response are associated with altered risk for Ureaplasma spp. respiratory colonization and BPD in preterm infants. METHODS: Twenty-four tag single nucleotide polymorphisms (SNPs) from Toll-like receptor (TLR)1, TLR2, TLR4 and TLR6 were assayed in 298 infants <33 weeks gestation who had serial respiratory cultures for Ureaplasma spp. and were evaluated for BPD. RESULTS: The majority of subjects (N = 205 [70%]) were African-American. One hundred ten (37%) were Ureaplasma positive. Four SNPs in TLR2 and TLR6 were significantly associated with Ureaplasma respiratory tract colonization. Single SNPs in TLR2, TLR4 and TLR6 were associated with BPD. TLR6 SNP rs5743827 was associated with both a decreased risk for Ureaplasma respiratory tract colonization and decreased risk for BPD (odds ratio: 0.54 [0.34-0.86] and odds ratio: 0.54 [0.31-0.95], respectively). There was a significant additive interaction between Ureaplasma colonization and genotype at TLR6 SNP rs5743827 (Padditive = 0.023), with an attributable proportion due to interaction of 0.542. CONCLUSIONS: Polymorphisms in host defense genes may alter susceptibility to Ureaplasma infection and severity of the inflammatory response contributing to BPD. These observations implicate host genetic susceptibility as a major factor in BPD pathogenesis in Ureaplasma-infected preterms.

AB - BACKGROUND: Ureaplasma spp. respiratory tract colonization is a risk factor for bronchopulmonary dysplasia (BPD) in preterm infants, but differences in host susceptibility have not been elucidated. We hypothesized that variants in genes regulating the innate immune response are associated with altered risk for Ureaplasma spp. respiratory colonization and BPD in preterm infants. METHODS: Twenty-four tag single nucleotide polymorphisms (SNPs) from Toll-like receptor (TLR)1, TLR2, TLR4 and TLR6 were assayed in 298 infants <33 weeks gestation who had serial respiratory cultures for Ureaplasma spp. and were evaluated for BPD. RESULTS: The majority of subjects (N = 205 [70%]) were African-American. One hundred ten (37%) were Ureaplasma positive. Four SNPs in TLR2 and TLR6 were significantly associated with Ureaplasma respiratory tract colonization. Single SNPs in TLR2, TLR4 and TLR6 were associated with BPD. TLR6 SNP rs5743827 was associated with both a decreased risk for Ureaplasma respiratory tract colonization and decreased risk for BPD (odds ratio: 0.54 [0.34-0.86] and odds ratio: 0.54 [0.31-0.95], respectively). There was a significant additive interaction between Ureaplasma colonization and genotype at TLR6 SNP rs5743827 (Padditive = 0.023), with an attributable proportion due to interaction of 0.542. CONCLUSIONS: Polymorphisms in host defense genes may alter susceptibility to Ureaplasma infection and severity of the inflammatory response contributing to BPD. These observations implicate host genetic susceptibility as a major factor in BPD pathogenesis in Ureaplasma-infected preterms.

KW - Toll-like receptor 6

KW - Ureaplasma parvum

KW - Ureaplasma urealyticum

KW - single nucleotide polymorphism

UR - http://www.scopus.com/inward/record.url?scp=84880644370&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84880644370&partnerID=8YFLogxK

U2 - 10.1097/INF.0b013e31828fc693

DO - 10.1097/INF.0b013e31828fc693

M3 - Article

C2 - 23518821

AN - SCOPUS:84880644370

VL - 32

SP - 898

EP - 904

JO - Pediatric Infectious Disease Journal

JF - Pediatric Infectious Disease Journal

SN - 0891-3668

IS - 8

ER -