Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy.
Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy.
复制标题
DOI：
10.1016/j.jaci.2011.01.031
复制
发表时间：
2011-03
期刊：
影响因子：
--
通讯作者：
McLean WH
中科院分区：
文献类型：
--
作者：
Brown SJ;Asai Y;Cordell HJ;Campbell LE;Zhao Y;Liao H;Northstone K;Henderson J;Alizadehfar R;Ben-Shoshan M;Morgan K;Roberts G;Masthoff LJ;Pasmans SG;van den Akker PC;Wijmenga C;Hourihane JO;Palmer CN;Lack G;Clarke A;Hull PR;Irvine AD;McLean WH
IgE介导的花生过敏是一个具有很强遗传力的复杂性状，但其遗传基础目前尚不清楚。聚丝蛋白基因内的功能缺失突变与特应性皮炎和其他特应性疾病相关;因此，聚丝蛋白是花生过敏病因学中的候选基因。探讨聚丝蛋白功能缺失突变与花生过敏的关系。对71例英国、荷兰和爱尔兰花生过敏的口服食物激发阳性患者和1000例非花生致敏的英国人群对照的病例对照研究。在390名患有花生过敏的白色加拿大患者（定义为食物激发或临床病史和皮肤点刺试验风团对花生≥8 mm和/或花生特异性IgE ≥15 kUL−1）和891名白色加拿大人群对照中进行了重复试验。在每个人群中检测了最常见的聚丝蛋白功能丧失突变：欧洲人中的R501 X和2282 del 4，加拿大人中的R501 X，2282 del 4，R2447 X和S3247 X。Fisher精确检验和逻辑回归用于检验相关性;协变量分析控制共存的特应性皮炎。在食物激发阳性患者中，聚丝蛋白功能缺失突变与花生过敏有很强的显著相关性（P = 3.0 × 10−6;比值比，5.3; 95%CI，2.8-10.2），这种相关性在加拿大研究中得到了复制（P = 5.4 × 10−5;比值比，1.9; 95%CI，1.4-2.6）。在控制了同时存在的特应性皮炎后，聚丝蛋白突变与花生过敏的相关性仍然显著（P = 0.0008）。聚丝蛋白突变是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这种疾病的发病机制中起作用。
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.
登录
查看更多内容
影响因子：
14.2
作者：
Oyoshi, Michiko K.;Murphy, George F.;Geha, Raif S.
通讯作者：
Geha, Raif S.
影响因子：
6.5
作者：
Man, Mao-Qiang;Hatano, Yutaka;Elias, Peter M.
通讯作者：
Elias, Peter M.
影响因子：
14.2
作者：
Roberts, G;Lack, G
通讯作者：
Lack, G
影响因子：
4.4
作者：
Shamssain, Mohammed
通讯作者：
Shamssain, Mohammed
影响因子：
14.2
作者：
Boyce, Joshua A.;Assa'ad, Amal;Burks, A. Wesley;Jones, Stacie M.;Sampson, Hugh A.;Wood, Robert A.;Plaut, Marshall;Cooper, Susan F.;Fenton, Matthew J.;Arshad, S. Hasan;Bahna, Sami L.;Beck, Lisa A.;Byrd-Bredbenner, Carol;Camargo, Carlos A., Jr.;Eichenfield, Lawrence;Furuta, Glenn T.;Hanifin, Jon M.;Jones, Carol;Kraft, Monica;Levy, Bruce D.;Lieberman, Phil;Luccioli, Stefano;McCall, Kathleen M.;Schneider, Lynda C.;Simon, Ronald A.;Simons, F. Estelle R.;Teach, Stephen J.;Yawn, Barbara P.;Schwaninger, Julie M.
通讯作者：
Schwaninger, Julie M.