Epithelial Genetics Group, Division of Molecular Medicine, University of Dundee, Dundee, United Kingdom.
J Allergy Clin Immunol. 2011 Mar;127(3):661-7. doi: 10.1016/j.jaci.2011.01.031.
IgE-mediated peanut allergy is a complex trait with strong heritability, but its genetic basis is currently unknown. Loss-of-function mutations within the filaggrin gene are associated with atopic dermatitis and other atopic diseases; therefore, filaggrin is a candidate gene in the etiology of peanut allergy.
To investigate the association between filaggrin loss-of-function mutations and peanut allergy.
Case-control study of 71 English, Dutch, and Irish oral food challenge-positive patients with peanut allergy and 1000 non peanut-sensitized English population controls. Replication was tested in 390 white Canadian patients with peanut allergy (defined by food challenge, or clinical history and skin prick test wheal to peanut ≥ 8 mm and/or peanut-specific IgE ≥ 15 kUL(-1)) and 891 white Canadian population controls. The most prevalent filaggrin loss-of-function mutations were assayed in each population: R501X and 2282del4 in the Europeans, and R501X, 2282del4, R2447X, and S3247X in the Canadians. The Fisher exact test and logistic regression were used to test for association; covariate analysis controlled for coexistent atopic dermatitis.
Filaggrin loss-of-function mutations showed a strong and significant association with peanut allergy in the food challenge-positive patients (P = 3.0 × 10(-6); odds ratio, 5.3; 95% CI, 2.8-10.2), and this association was replicated in the Canadian study (P = 5.4 × 10(-5); odds ratio, 1.9; 95% CI, 1.4-2.6). The association of filaggrin mutations with peanut allergy remains significant (P = .0008) after controlling for coexistent atopic dermatitis.
Filaggrin mutations represent a significant risk factor for IgE-mediated peanut allergy, indicating a role for epithelial barrier dysfunction in the pathogenesis of this disease.
IgE 介导的花生过敏是一种具有强遗传性的复杂特征，但它的遗传基础目前尚不清楚。角蛋白丝聚合蛋白基因的功能丧失突变与特应性皮炎和其他特应性疾病有关；因此，角蛋白丝聚合蛋白是花生过敏发病机制中的候选基因。
研究角蛋白丝聚合蛋白功能丧失突变与花生过敏之间的关系。
对 71 例经口食物激发试验阳性的患有花生过敏的英国、荷兰和爱尔兰患者以及 1000 例非花生致敏的英国人群对照进行病例对照研究。在 390 例加拿大白种人花生过敏患者（通过食物激发试验、或临床病史和皮试风团≥8mm 和/或花生特异性 IgE≥15kuL(-1)）和 891 例加拿大白种人人群对照中进行了复制试验。在每个人群中检测了最常见的角蛋白丝聚合蛋白功能丧失突变：欧洲人中的 R501X 和 2282del4，以及加拿大人中的 R501X、2282del4、R2447X 和 S3247X。采用 Fisher 精确检验和 logistic 回归检验进行关联分析；协变量分析控制了共存的特应性皮炎。
角蛋白丝聚合蛋白功能丧失突变与食物激发试验阳性患者的花生过敏有很强且显著的关联（P=3.0×10(-6)；优势比，5.3；95%可信区间，2.8-10.2），这一关联在加拿大研究中得到了复制（P=5.4×10(-5)；优势比，1.9；95%可信区间，1.4-2.6）。在控制共存特应性皮炎后，角蛋白丝聚合蛋白突变与花生过敏的关联仍然显著（P=0.0008）。
角蛋白丝聚合蛋白突变是 IgE 介导的花生过敏的一个重要危险因素，表明上皮屏障功能障碍在该疾病发病机制中起作用。
