Published ahead of print on April 13, 2006, doi:10.1164/rccm.200509-1380OC
Am. J. Respir. Crit. Care Med., Volume 174, Number 4, August 2006, 386-392
A more recent version of this article appeared on August 15, 2006
Submitted on September 6, 2005
Accepted on April 13, 2006
Endotoxin Exposure, CD14 and Allergic Disease: An Interaction between Genes and the Environment
Angela Simpson1, Sally L John2, Francine Jury2, Rob Niven1, Ashley Woodcock1, William ER Ollier2, and Adnan Custovic1*
1 Academic Division of Medicine and Surgery South, University of Manchester, North West Lung Centre, Wythenshawe Hospital, Manchester, United Kingdom,
2 Centre for Integrated Genomic Medical Research (CIGMR), University of Manchester, Manchester, United Kingdom
* To whom correspondence should be addressed. E-mail: adnan.custovic{at}manchester.ac.uk.
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 CtoT) 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 CtoT; rs2569190). We assessed children for allergic sensitization (IgE>0.2kU/L to at least one of 7 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, 95% confidence intervals 0.95, 0.71-1.23, p=0.7 and 0.90, 0.77-1.04, p=0.16 respectively) or endotoxin and eczema (0.99, 0.81-1.20, p=0.89; 1.38, 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 (0.70, 0.55-0.89, p=0.004) and eczema (0.73, 0.56-0.95, p=0.02). However, we observed an increased risk of non-atopic wheeze with increasing endotoxin exposure in CC children (1.42, 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 increased risk of non-atopic wheeze in children with CC genotype at -159 of the CD14 gene. The impact of environmental endotoxin may be enhanced in individuals with this genotype.
Key words: genetics, allergy, asthma
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