Imboden M, Nicod L, Nieters A, Glaus E, Matyas G, Bircher A J, Ackermann-Liebrich U, Berger W, Probst-Hensch N M
Molecular Epidemiology/Cancer Registry, Institutes of Social and Preventive Medicine & Clinical Pathology, Zurich, Switzerland.
Clin Exp Allergy. 2006 Feb;36(2):211-8. doi: 10.1111/j.1365-2222.2006.02424.x.
IL-18 is a pleiotrophic cytokine involved in both, T-helper type 1 (Th1) and Th2 differentiation. Recently genetic variants in the IL-18 gene have been associated with increased risk of atopy and asthma.
To examine the relationship of a genetic, haplotype-tagging promotor variant -137G/C in the IL-18 gene with atopic asthma in a large, well-characterized and population-based study of adults.
Prospective cohort study design was used to collect interview and biological measurement data at two examination time-points 11 years apart. Multivariate logistic regression analysis was used to assess the association of genotype with asthma and atopy.
The G-allele of the IL-18 promotor variant (-137G/C) was associated with a markedly increased risk for the prevalence of physician-diagnosed asthma with concomitant skin reactivity to common allergens. Stratification of the asthma cases by skin reactivity to common allergens revealed an exclusive association of IL-18 -137 G-allele with an increased prevalence of atopic asthma (adjusted odds ratio (OR): 3.63; 95% confidence interval: (1.64-8.02) for GC or GG carriers vs. CC carriers), and no according association with asthma and concomitant negative skin reactivity (adjusted OR: 1.13; 0.66-1.94). The interaction between IL-18 -137G/C genotype and positive skin prick test was statistically significant (P=0.029). None of 74 incident asthma cases with atopy at baseline exhibited the CC genotype.
Our results strongly suggest that this variant of the IL-18 gene is an important genetic determinant involved in the development of atopic asthma.
白细胞介素-18（IL-18）是一种多效性细胞因子，参与1型辅助性T细胞（Th1）和Th2细胞分化。最近，IL-18基因的遗传变异与特应性和哮喘风险增加有关。
在一项针对成年人的大型、特征明确的基于人群的研究中，研究IL-18基因中一个基因单倍型标签启动子变异-137G/C与特应性哮喘的关系。
采用前瞻性队列研究设计，在相隔11年的两个检查时间点收集访谈和生物学测量数据。采用多因素逻辑回归分析评估基因型与哮喘和特应性的关联。
IL-18启动子变异（-137G/C）的G等位基因与医生诊断的哮喘患病率显著增加相关，同时伴有对常见过敏原的皮肤反应性。根据对常见过敏原的皮肤反应性对哮喘病例进行分层，发现IL-18 -137 G等位基因与特应性哮喘患病率增加存在唯一关联（GC或GG携带者与CC携带者相比，调整后的优势比（OR）：3.63；95%置信区间：（1.64 - 8.02）），与哮喘及伴有阴性皮肤反应性无相应关联（调整后的OR：1.13；0.66 - 1.94）。IL-18 -137G/C基因型与阳性皮肤点刺试验之间的相互作用具有统计学意义（P = 0.029）。74例基线时有特应性的新发哮喘病例中，无一例表现为CC基因型。
我们的结果强烈表明，IL-18基因的这种变异是参与特应性哮喘发生发展的重要遗传决定因素。
