Endotoxin exposure, CD14, and allergic disease: an interaction between genes and the environment

Am J Respir Crit Care Med. 2006 Aug 15;174(4):386-92. doi: 10.1164/rccm.200509-1380OC. Epub 2006 Apr 13.


Rationale: High endotoxin exposure may reduce the risk of allergic sensitization.

Objective: To determine the relationship between a promoter polymorphism in the CD14 gene (CD14/-159 C to T) and endotoxin exposure in relation to the development of allergic sensitization, eczema, and wheeze within the setting of a birth cohort.

Methods: We genotyped 442 children (CD14/-159 C to T; rs2569190). We assessed children for allergic sensitization (IgE > 0.2 kU/L to at least one of seven allergens), eczema (physical examination), and parentally reported wheeze. Endotoxin was measured in house dust.

Main results: Genotype frequencies were consistent with other populations (TT, 25%; CT, 47%; CC, 28%). Sensitization (present in 33% of children) was not associated with genotype. For children with TT and CT genotypes, there was no association between endotoxin and sensitization (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.71-1.23; p = 0.7; and OR, 0.90; 95% CI, 0.77-1.04; p = 0.16, respectively) or endotoxin and eczema (OR, 0.99; 95% CI, 0.81-1.20; p = 0.89; and OR, 1.38; 95% CI, 0.83-2.30; p = 0.22, respectively). In children with the genotype CC, increasing endotoxin load was associated with a marked and significant reduction in the risk of sensitization (OR, 0.70; 95% CI, 0.55-0.89; p = 0.004) and eczema (OR, 0.73; 95% CI, 0.56-0.95; p = 0.02). However, we observed an increased risk of nonatopic wheeze with increasing endotoxin exposure in children with the CC genotype (OR, 1.42; 95% CI, 1.01-1.99; p = 0.04) but not other genotypes. No effect was seen for atopic wheeze.

Conclusions: Increasing endotoxin exposure is associated with reduced risk of allergic sensitization and eczema but with increased risk of nonatopic wheeze in children with the CC genotype at -159 of the CD14 gene. The impact of environmental endotoxin may be enhanced in individuals with this genotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asthma / genetics*
  • Asthma / immunology
  • Child, Preschool
  • Eczema / genetics
  • Eczema / immunology
  • Eczema / physiopathology
  • Endotoxins / analysis*
  • Female
  • Genetic Predisposition to Disease / epidemiology
  • Humans
  • Lipopolysaccharide Receptors / genetics*
  • Male
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic / physiology*
  • Pyroglyphidae / immunology
  • Respiratory Sounds / genetics
  • Risk Factors
  • Toll-Like Receptor 4 / genetics


  • Endotoxins
  • Lipopolysaccharide Receptors
  • Toll-Like Receptor 4