Leynaert Bénédicte, Guilloud-Bataille Monique, Soussan David, Benessiano Joëlle, Guénégou Armelle, Pin Isabelle, Neukirch Françoise
Institut National de la Santé et de la Recherche Médicale, Unit 700, Epidemiologie, Paris, France.
J Allergy Clin Immunol. 2006 Sep;118(3):658-65. doi: 10.1016/j.jaci.2006.06.015. Epub 2006 Jul 28.
A higher exposure to bacterial compounds is purported to explain the lower prevalence of allergy in farm children, but responsiveness to bacterial compounds is modulated by genetic factors.
To assess whether the protective effect of farm exposure on atopy is influenced by a CD14 promoter functional polymorphism.
We administered a detailed questionnaire on farm exposure in childhood and genotyped the CD14 C-159T polymorphism in 2 French centers participating in the European Community Respiratory Health Survey (ECRHS)-II.
Six hundred randomly selected young adults provided blood samples for IgE measurements and had CD14 C-159T genotyped. Exposure to a farming environment in early life was associated with a reduced risk of nasal allergies (odds ratio [OR], 0.54; 95% CI, 0.29-1.00) and atopic sensitization (OR, 0.47; 95% CI, 0.24-0.93) in adulthood. A lower risk of allergic rhinitis and atopy was also observed in carriers of the CD14-159TT genotype compared with -159CC subjects (OR, 0.52; 95% CI, 0.30-0.88; and OR, 0.54; 95% CI, 0.31-0.92, respectively). When farm exposure and CD14 C-159T were considered together, the risk of nasal allergies and atopy was the most reduced in the subjects who combined both an early-life exposure to a farming environment and the -159TT genotype (OR, 0.26; 95% CI, 0.07-0.94; and OR, 0.21; 95% CI, 0.05-0.93, respectively, vs nonexposed -159CC+CT subjects). The results were consistent in the 2 centers, supporting the validity of the results.
A gene-by-environment interaction between CD14 C-159T and environmental exposure in childhood may modify the development of atopy.
This polymorphism should be considered in interventions studies that use microbial stimuli to reduce sensitization.
据推测,较高水平的细菌化合物暴露可解释农场儿童过敏患病率较低的现象,但对细菌化合物的反应性受遗传因素调节。
评估儿童期农场暴露对特应性的保护作用是否受CD14启动子功能多态性的影响。
我们在参与欧洲共同体呼吸健康调查(ECRHS)-II的2个法国中心,就儿童期农场暴露情况进行了详细问卷调查,并对CD14 C-159T多态性进行了基因分型。
600名随机选取的年轻人提供了血液样本用于检测IgE,并对CD14 C-159T进行了基因分型。早年暴露于农场环境与成年后患鼻过敏的风险降低相关(比值比[OR],0.54;95%可信区间[CI],0.29-1.00)以及特应性致敏风险降低相关(OR,0.47;95%CI,0.24-0.93)。与-159CC受试者相比,CD14-159TT基因型携带者患过敏性鼻炎和特应性的风险也较低(分别为OR,0.52;95%CI,0.30-0.88;以及OR,0.54;95%CI,0.31-0.92)。当同时考虑农场暴露和CD14 C-159T时,早年暴露于农场环境且具有-159TT基因型的受试者患鼻过敏和特应性的风险降低最为显著(分别为OR,0.26;95%CI,0.07-0.94;以及OR,0.21;95%CI,0.05-0.93,与未暴露的-159CC+CT受试者相比)。两个中心的结果一致,支持了结果的有效性。
CD14 C-159T与儿童期环境暴露之间的基因-环境相互作用可能会改变特应性的发展。
在使用微生物刺激来降低致敏的干预研究中应考虑这种多态性。