engleski

Opposite effect of endotoxin exposure with different MD-2 genotypes on asthma in children

Background: Endotoxin exposure may play an important role in the development of asthma. MD-2 is a glycoprotein that assembles with TLR4 to form functional signalling receptor for endotoxin. We hypothesised that genetic variations in MD-2 may modify the relationship between endotoxin exposure and asthma. Methods: Study population comprised 423 children with physician-diagnosed asthma and 414 non-asthmatic controls (age 6-18 years) recruited from the general hospital in Slavonski Brod, Croatia. We collected mattress dust sample and measured endotoxin content using kinetic limulus assay. We genotyped 9 haplotype-tagging SNPs in MD-2 (Sequenom). Correction for multiple comparisons was carried out using Benjamini- Hochberg’s False Discovery Rate (FDR) method. Results: In the whole population, endotoxin exposure was associated with a decreased risk of asthma (aOR 0.75, 95%CI 0.58-0.98, p=0.03). None of the MD-2 SNPs was associated with asthma after FDR correction. For three SNPs we identified a significant interaction between genotype and endotoxin exposure (rs7822054, rs7822407 and rs11786591 ; pint<0.02), in that increasing endotoxin load was protective against asthma in some genotype groups, but the association tended to be in the opposite direction amongst children with other genotypes. For example, for rs7822054, amongst children carrying A allele endotoxin exposure was protective (aOR 0.71, 95%CI 0.46- 1.00), but amongst G allele homozygotes it increased the risk of asthma (aOR 2.64, 95%CI 1.09-6.38 ; FDR corrected pint=0.03). Conclusion: The effect of endotoxin exposure on asthma may differ among children with different variants of the MD2 gene.

MD-2; asthma; endotoxin; gene-environment interaction

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