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Endotoxin Exposure, CD14 and Allergic Disease: An Interaction between Genes and the Environment.
Simpson A, John S, Jury F, Niven R, Niven RR M, Woodcock AA, Ollier WER, Custovic A
Am J Respir Crit Care Med. 2006;174(4):386-392.
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Abstract
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.