Department of Dermatology, Innsbruck Medical University, Innsbruck, Austria.
Wien Klin Wochenschr. 2010 Oct;122(19-20):551-7. doi: 10.1007/s00508-010-1449-3. Epub 2010 Sep 27.
Recent studies have shown an association of loss-of-function mutations in the filaggrin gene (FLG) with ichthyosis vulgaris and atopic eczema (AE). Case selection may have distorted the hitherto reported prevalence of FLG mutations and their relation to atopic disease. The aim of the study was to determine the true population prevalence of FLG mutations in unselected children with and without reported physician diagnoses of asthma, allergic rhinitis and AE and their relationship with family history of atopic disease.
We used a nested case-control design by sampling children with reported doctor's diagnoses of AE, asthma and allergic rhinitis and randomly selected controls from a larger cross-sectional study (n = 1263). Most common FLG mutations R501X, 2282del4, and R2447X were screened in DNA extracted from defrosted urine samples. The relationship of the combined FLG variants with atopic diseases and with reported family history of AE, asthma, and rhinitis was assessed.
In the patient group one homozygote (R501X/R501X), 4 compound heterozygotes (3 R501X/2282del4, one 2282del4/R2447X), and 17 heterozygotes (10 R501X/wt, 5 2282del4/wt, and 2 R2447X/wt), in the control group 9 heterozygotes (5 R501X/wt, 4 2282del4/wt) were detected. The combined prevalence of FLG loss-of-function alleles was 5% in the control group and 9% in the atopic sample. In a subgroup analysis, the combination of allergic rhinitis and AE showed a significant relationship with FLG mutations, OR = 3.7 (1.01-12.67, p = 0.024). Likewise, significant relations with reported family history of asthma, OR = 4.35 (1.78-10.62, p = 0.0012), allergic rhinitis, OR = 2.33 (1.49-3.63, p = 0.0002), and AE, OR = 5.08 (2.78-9.30, p ≤ 0.0001) were observed. In contrast to clinical studies with higher percentages of severely affected persons, FLG mutations here showed a moderate association with atopic disease.
Case selection may be responsible for overestimating the prevalence of FLG mutations in atopic disease.
最近的研究表明，角蛋白丝聚合蛋白基因（FLG）的功能丧失突变与寻常型鱼鳞病和特应性皮炎（AE）有关。病例选择可能会扭曲迄今为止报告的 FLG 突变的流行率及其与特应性疾病的关系。本研究的目的是确定未经选择的伴有或不伴有医生诊断的哮喘、过敏性鼻炎和 AE 的儿童中 FLG 突变的真实人群流行率及其与特应性疾病家族史的关系。
我们使用嵌套病例对照设计，从一项较大的横断面研究（n=1263）中随机选择有 AE、哮喘和过敏性鼻炎医生诊断报告的儿童作为病例，并选择对照组。从解冻的尿液样本中提取 DNA，筛查最常见的 FLG 突变 R501X、2282del4 和 R2447X。评估合并的 FLG 变体与特应性疾病以及报告的 AE、哮喘和鼻炎家族史的关系。
在患者组中，发现 1 名纯合子（R501X/R501X）、4 名复合杂合子（3 名 R501X/2282del4，1 名 2282del4/R2447X）和 17 名杂合子（10 名 R501X/wt、5 名 2282del4/wt 和 2 名 R2447X/wt），在对照组中，检测到 9 名杂合子（5 名 R501X/wt、4 名 2282del4/wt）。FLG 功能丧失等位基因的合并患病率在对照组中为 5%，在特应性样本中为 9%。在亚组分析中，过敏性鼻炎和 AE 的组合与 FLG 突变呈显著相关，OR=3.7（1.01-12.67，p=0.024）。同样，与报告的哮喘家族史、OR=4.35（1.78-10.62，p=0.0012）、过敏性鼻炎、OR=2.33（1.49-3.63，p=0.0002）和 AE，OR=5.08（2.78-9.30，p≤0.0001）也有显著关系。与具有较高严重程度患者百分比的临床研究相比，FLG 突变在此与特应性疾病呈中度相关。
病例选择可能导致特应性疾病中 FLG 突变的流行率高估。
