Simpson Angela, John Sally L, Jury Francine, Niven Rob, Woodcock Ashley, Ollier William E R, Custovic Adnan
North West Lung Centre, Wythenshawe Hospital, Manchester M23 9LT, UK.
Am J Respir Crit Care Med. 2006 Aug 15;174(4):386-92. doi: 10.1164/rccm.200509-1380OC. Epub 2006 Apr 13.
High endotoxin exposure may reduce the risk of allergic sensitization.
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.
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.
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.
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.
高内毒素暴露可能降低过敏致敏风险。
确定出生队列中，CD14基因启动子多态性（CD14 / -159 C至T）与内毒素暴露之间的关系，及其与过敏致敏、湿疹和喘息发生的关系。
我们对442名儿童（CD14 / -159 C至T；rs2569190）进行基因分型。我们评估儿童的过敏致敏情况（针对七种过敏原中至少一种的IgE> 0.2 kU/L）、湿疹（体格检查）以及家长报告的喘息情况。测定室内灰尘中的内毒素含量。
基因型频率与其他人群一致（TT，25％；CT，47％；CC，28％）。致敏情况（33％的儿童存在）与基因型无关。对于TT和CT基因型的儿童，内毒素与致敏之间无关联（优势比[OR]，0.95；95％置信区间[CI]，0.71 - 1.23；p = 0.7；以及OR，0.90；95％CI，0.77 - 1.04；p = 0.16），内毒素与湿疹之间也无关联（OR，0.99；95％CI，0.81 - 1.20；p = 0.89；以及OR，1.38；95％CI，0.83 - 2.30；p = 0.22）。对于CC基因型的儿童，内毒素负荷增加与致敏风险显著降低相关（OR，0.70；95％CI，0.55 - 0.89；p = 0.004），与湿疹风险降低相关（OR，0.73；95％CI，0.56 - 0.95；p = 0.02）。然而，我们观察到CC基因型儿童中，随着内毒素暴露增加，非特应性喘息风险增加（OR，1.42；95％CI，1.01 - 1.99；p = 0.04），而其他基因型儿童未观察到这种情况。特应性喘息未见影响。
内毒素暴露增加与过敏致敏和湿疹风险降低相关，但与CD14基因-159位点CC基因型儿童的非特应性喘息风险增加相关。这种基因型个体中环境内毒素的影响可能会增强。
