HLA-DQ and RBFOX1 as susceptibility genes for an outbreak of hydrolyzed wheat allergy
HLA-DQ and RBFOX1 as susceptibility genes for an outbreak of hydrolyzed wheat allergy
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DOI：
10.1016/j.jaci.2019.06.034
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发表时间：
2019-11-01
影响因子：
14.2
通讯作者：
Matsunaga, Kayoko
中科院分区：
文献类型：
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作者：
Noguchi, Emiko;Akiyama, Masato;Matsunaga, Kayoko
背景资料：食物过敏是世界范围内日益严重的健康问题，因为它的患病率越来越高，危及生命的潜力，以及缺乏有效的预防治疗。在日本的一次小麦过敏爆发中，数千名患者在使用含有水解小麦蛋白（HWP）的肥皂后对小麦产生过敏反应。目的：本研究的目的是调查可能导致HWP过敏敏感性的遗传变异。方法：我们在452例病例和2700例对照受试者中进行了一项HWP过敏的全基因组关联研究，使用了660万个基因分型或插补的单核苷酸多态性。通过对45名HWP过敏患者和326名对照受试者的独立样本进行单核苷酸多态性基因分型来评估复制。通过全基因组关联研究，我们确定了6p 21上的II类HLA区域的显著关联，（对于rs 9271588，P = 2.16 X 10（-24）;对于HLA-DQ α 1氨基酸位置34，P = 2.96 X 10（-24））和RBFOX 1基因座在16 p13（rs74575857，P = 8.4 X 10（-9））。在复制数据集中也证实了这种关联。HLA-DQ分子P4结合口袋中的两个氨基酸多态性（HLA-DQ β 1第13和26位氨基酸）均达到全基因组显著水平（P < 5.0 × 10（-8））。结论：我们的数据首次证明了HWP过敏的遗传风险，并表明这种遗传风险主要表现为HLA变体的多种组合。
Background: Food allergy is a growing health problem worldwide because of its increasing prevalence, life-threatening potential, and shortage of effective preventive treatments. In an outbreak of wheat allergy in Japan, thousands of patients had allergic reactions to wheat after using soap containing hydrolyzed wheat protein (HWP).Objectives: The aim of the present study was to investigate genetic variation that can contribute to susceptibility to HWP allergy.Methods: We conducted a genome-wide association study of HWP allergy in 452 cases and 2700 control subjects using 6.6 million genotyped or imputed single nucleotide polymorphisms. Replication was assessed by genotyping single nucleotide polymorphisms in independent samples comprising 45 patients with HWP allergy and 326 control subjects.Results: Through the genome-wide association study, we identified significant associations with the class II HLA region on 6p21 (P = 2.16 X 10(-24) for rs9271588 and P = 2.96 X 10(-24) for HLA-DQ alpha 1 amino acid position 34) and with the RBFOX1 locus at 16p13 (rs74575857, P = 8.4 X 10(-9)). The associations were also confirmed in the replication data set. Both amino acid polymorphisms (HLA-DQ beta 1 amino acid positions 13 and 26) located in the P4 binding pockets on the HLA-DQ molecule achieved the genome-wide significance level (P < 5.0 X 10(-8) ).Conclusions: Our data provide the first demonstration of genetic risk for HWP allergy and show that this genetic risk is mainly represented by multiple combinations of HLA variants.