Elder siblings enhance the effect of filaggrin mutations on childhood eczema: Results from the 2 birth cohort studies LISAplus and GINIplus
Elder siblings enhance the effect of filaggrin mutations on childhood eczema: Results from the 2 birth cohort studies LISAplus and GINIplus
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DOI：
10.1016/j.jaci.2010.03.036
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发表时间：
2010-06-01
影响因子：
14.2
通讯作者：
Kraemer, Ursula
中科院分区：
文献类型：
--
作者：
Cramer, Claudia;Link, Elke;Kraemer, Ursula
背景：一些研究表明，年长的兄弟姐妹对湿疹的发展具有保护作用，这与卫生假说一致。然而，研究结果并不一致，湿疹的发展可能存在不同的因果途径。特别是屏障障碍，发现在儿童中的聚丝蛋白基因（FLG）的突变似乎发挥了重要的作用。Objective. To调查FLG突变和存在的哥哥姐姐对湿疹的发展在2个独立的birth cohols.Methods之间的相互作用：我们使用的数据从2个德国出生coholts（LISAplus，GINIplus）的6岁。在1039名（LISAplus）和1828名（GINIplus）儿童中进行了FLG突变（R501 X，2282 del 4）的基因分型。湿疹（诊断和症状）和年长的兄弟姐妹的数据通过父母问卷获得。湿疹，FLG基因突变，和哥哥姐姐之间的关联进行了纵向分析，通过使用广义估计equations.Results：我们发现没有保护作用的哥哥姐姐湿疹的发展。相反，如果有哥哥姐姐，FLG突变的儿童患湿疹的风险明显更高。参加日托中心减轻了这种影响。排除303名参加早期日托的儿童后，LISAplus和GINIplus中FLG基因突变和年长兄弟姐妹之间相互作用的比值比分别为3.27（95%CI，1.14-9.36）和2.41（95%CI，1.06-5.48）。如果有年长的兄弟姐妹，聚丝蛋白缺乏的儿童湿疹的患病率更高。我们的研究结果为复杂的皮肤驱动的致病机制提供了证据，这些机制可能因儿童的遗传背景而异。（J Allergy Clin Immunol 2010;125：1254-60.）
Background: Several studies showed a protective effect of elder siblings on eczema development, which is in line with the hygiene hypothesis. However, findings are not consistent, and there might exist different causal pathways for the development of eczema. Especially barrier disturbances as found in children with mutations in the filaggrin gene (FLG) seem to play an important role.Objectives: To investigate the interaction between FLG mutations and the presence of elder siblings on the development of eczema in 2 independent birth cohorts.Methods: We used data from 2 German birth cohorts (LISAplus, GINIplus) up to the age of 6 years. Genotyping for FLG mutations (R501X, 2282del4) was performed in 1039 (LISAplus) and 1828 (GINIplus) children. Data on eczema (diagnosis and symptoms) and elder siblings were obtained by parental questionnaires. The association among eczema, FLG mutations, and elder siblings was analyzed longitudinally by using generalized estimating equations.Results: We found no protective effect of elder siblings on eczema development. On the contrary, children with FLG mutations had a significantly higher risk for eczema if they had elder siblings. Attending day care centers lessened this effect. After excluding 303 children who attended early day care, the odds ratio for interaction between FLG mutations and elder siblings was 3.27 (95% CI, 1.14-9.36) in LISAplus and 2.41 (95% Cl, 1.06-5.48) in GINIplus.Conclusion: Our findings did not confirm a protective sibling effect. The prevalence of eczema in children with filaggrin deficiency was higher if elder siblings were present. Our results give evidence for complex skin-driven pathogenic mechanisms that might be different depending on children's genetic backgrounds. (J Allergy Clin Immunol 2010;125:1254-60.)