Cytokine gene polymorphisms and atopic disease in two European cohorts. (ECRHS-Basel and SAPALDIA).
Cytokine gene polymorphisms and atopic disease in two European cohorts. (ECRHS-Basel and SAPALDIA).
复制标题
DOI：
10.1186/1476-7961-4-9
复制
发表时间：
2006-06-07
期刊：
影响因子：
--
通讯作者：
Probst-Hensch, N M
中科院分区：
文献类型：
--
作者：
Imboden, M;Nieters, A;Probst-Hensch, N M
背景：特应性和过敏性表型的生物学特征是T辅助细胞反应失衡，偏向于与血清免疫球蛋白E(IgE)水平升高相关的2型(TH2)免疫反应。细胞因子基因的多态可能调节TH1/TH2平衡。因此，我们的目标是在两个可比较的研究人群中重现我们先前在欧洲研究人群中关于不同细胞因子多态性与自我报告的花粉热以及总IgE和特异性IgE水平升高的关系的研究结果。在欧洲共同体呼吸健康调查(ECRHS)的巴塞尔中心(ECRHS，n=418)，对10种不同的与功能相关的细胞因子基因多态进行了基因分型。在瑞士关于空气污染与成人肺部疾病的队列研究(SAPALDIA，n=6003)中，对两个细胞因子基因多态进行了分型。结果：我们确定IL4、IL10、IL6和IL18为特应性健康结局的候选基因。在大的、特征良好的SAPALDIA队列中，IL6(-174G&gT；C)和IL18(-137G>；C)多态与花粉热受试者循环总IgE浓度相关。IL18(-137G>；C)基因多态也与花粉热的流行有关。结论：现在需要对扩大的细胞因子候选基因区域的遗传变异进行全面的描述。大型研究网络必须跟进，以调查由遗传易感和环境风险因素定义的风险模式与特定特应性表型的关联。
BACKGROUND: Atopy and allergic phenotypes are biologically characterized by an imbalanced T helper cell response skewed towards a type 2 (TH2) immune response associated with elevated serum immunoglobulin E (IgE) levels. Polymorphisms in cytokine genes might modulate regulation of the TH1/TH2 balance. We thus aimed at reproducing our previous findings from a European study population on the association of various cytokine polymorphisms with self-reported hay fever as well as increased total and specific IgE levels in two comparable study populations.METHODS: Two prospective Caucasian cohorts were used. In the Basel center of the European Community Respiratory Health Survey (ECRHS, n = 418) ten distinct cytokine polymorphisms of putative functional relevance were genotyped. In the Swiss cohort Study on Air Pollution And Lung Disease In Adults (SAPALDIA, n = 6003) two cytokine polymorphisms were genotyped. The associations of these polymorphisms with atopy were estimated by covariance and logistic regression analysis.RESULTS: We confirmed IL4, IL10, IL6 and IL18 as candidate genes for atopic health outcomes. In the large, well-characterized SAPALDIA cohort the IL6(-174G>C) and IL18(-137G>C) polymorphisms were associated with circulating total IgE concentrations in subjects with hay fever. The IL18(-137G>C) polymorphism was also associated with the prevalence of hay fever.CONCLUSION: Comprehensive characterization of genetic variation in extended cytokine candidate gene regions is now needed. Large study networks must follow to investigate the association of risk patterns defined by genetic predisposing and environmental risk factors with specific atopic phenotypes.