Kahr Niklas, Naeser Vibeke, Stensballe Lone Graff, Kyvik Kirsten Ohm, Skytthe Axel, Backer Vibeke, Bønnelykke Klaus, Thomsen Simon Francis
Department of Respiratory Medicine, Bispebjerg Hospital, Copenhagen, Denmark.
Clin Respir J. 2015 Jan;9(1):79-86. doi: 10.1111/crj.12110. Epub 2014 Feb 24.
The development of atopic diseases early in life suggests an important role of perinatal risk factors.
To study whether early-life exposures modify the genetic influence on atopic diseases in a twin population.
Questionnaire data on atopic diseases from 850 monozygotic and 2279 like-sex dizygotic twin pairs, 3-9 years of age, from the Danish Twin Registry were cross-linked with data on prematurity, Cesarean section, maternal age at birth, parental cohabitation, season of birth and maternal smoking during pregnancy, from the Danish National Birth Registry. Significant predictors of atopic diseases were identified with logistic regression and subsequently tested for genetic effect modification using variance components analysis.
After multivariable adjustment, prematurity (gestational age below 32 weeks) [odds ratio (OR) = 1.93, confidence interval (CI) = 1.45-2.56], Cesarean section (OR = 1.25, CI = 1.05-1.49) and maternal smoking during pregnancy (OR = 1.70, CI = 1.42-2.04) significantly influenced the risk of asthma, whereas none of the factors were significantly associated with atopic dermatitis and hay fever. Variance components analysis stratified by exposure status showed no significant change in the heritability of asthma according to the identified risk factors.
In this population-based study of children, there was no evidence of genetic effect modification of atopic diseases by several identified early-life risk factors. The causal relationship between these risk factors and atopic diseases may therefore be mediated via mechanisms different from gene-environment interaction.
特应性疾病在生命早期的发展表明围产期危险因素起着重要作用。
研究生命早期暴露是否会改变双生子群体中基因对特应性疾病的影响。
从丹麦双生子登记处选取850对单卵双生子和2279对同性双卵双生子（年龄3至9岁），获取有关特应性疾病的问卷数据，并与丹麦国家出生登记处的早产、剖宫产、母亲生育年龄、父母同居情况、出生季节以及孕期母亲吸烟等数据进行交叉关联。通过逻辑回归确定特应性疾病的显著预测因素，随后使用方差成分分析检验基因效应修饰情况。
经过多变量调整后，早产（孕周低于32周）[比值比（OR）=1.93，置信区间（CI）=1.45 - 2.56]、剖宫产（OR = 1.25，CI = 1.05 - 1.49）以及孕期母亲吸烟（OR = 1.70，CI = 1.42 - 2.04）对哮喘风险有显著影响，而这些因素均与特应性皮炎和花粉症无显著关联。按暴露状态分层的方差成分分析显示，根据所确定的危险因素，哮喘的遗传度无显著变化。
在这项基于人群的儿童研究中，没有证据表明几种已确定的生命早期危险因素会对特应性疾病产生基因效应修饰。因此，这些危险因素与特应性疾病之间的因果关系可能是通过不同于基因 - 环境相互作用的机制介导的。
