Department of Medical Genetics, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Department of Ophthalmology, Graduate school of Medical Sciences, Kyushu University, Fukuoka, Japan.
J Allergy Clin Immunol. 2019 Nov;144(5):1354-1363. doi: 10.1016/j.jaci.2019.06.034. Epub 2019 Jul 10.
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).
The aim of the present study was to investigate genetic variation that can contribute to susceptibility to HWP allergy.
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.
Through the genome-wide association study, we identified significant associations with the class II HLA region on 6p21 (P = 2.16 × 10 for rs9271588 and P = 2.96 × 10 for HLA-DQα1 amino acid position 34) and with the RBFOX1 locus at 16p13 (rs74575857, P = 8.4 × 10). The associations were also confirmed in the replication data set. Both amino acid polymorphisms (HLA-DQβ1 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 × 10).
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.
由于食物过敏的发病率不断上升、具有潜在的致命性以及缺乏有效的预防治疗方法，食物过敏已成为全球日益严重的健康问题。在日本的一次小麦过敏爆发中，数千名使用含水解小麦蛋白（HWP）的肥皂的患者出现了过敏反应。
本研究旨在探讨可能导致对 HWP 过敏的遗传变异。
我们使用 660 万个经基因分型或推断的单核苷酸多态性对 452 例 HWP 过敏患者和 2700 例对照进行了 HWP 过敏的全基因组关联研究。通过对包含 45 例 HWP 过敏患者和 326 例对照的独立样本中的单核苷酸多态性进行基因分型，评估了复制结果。
通过全基因组关联研究，我们在 6p21 上的 II 类 HLA 区域（rs9271588 的 P 值为 2.16×10，HLA-DQα1 氨基酸位置 34 的 P 值为 2.96×10）和 16p13 上的 RBFOX1 基因座（rs74575857，P 值为 8.4×10）发现了与 HWP 过敏显著相关的区域。这些关联在复制数据集中也得到了证实。位于 HLA-DQ 分子 P4 结合口袋的两个氨基酸多态性（HLA-DQβ1 氨基酸位置 13 和 26）达到了全基因组显著水平（P<5.0×10）。
我们的数据首次提供了 HWP 过敏遗传风险的证据，并表明这种遗传风险主要由多个 HLA 变体组合代表。
