HLA-DQ and RBFOX1 as susceptibility genes for an outbreak of hydrolyzed wheat allergy

Emiko Noguchi, Masato Akiyama, Akiko Yagami, Tomomitsu Hirota, Yukinori Okada, Zenichiro Kato, Reiko Kishikawa, Yuma Fukutomi, Michihiro Hide, Eishin Morita, Michiko Aihara, Makiko Hiragun, Yuko Chinuki, Takahiro Okabe, Akiko Ito, Atsuko Adachi, Atsushi Fukunaga, Yumiko Kubota, Toshiyuki Aoki, Youko AokiKazue Nishioka, Tetsuya Adachi, Nobuo Kanazawa, Hitoshi Miyazawa, Hiroyuki Sakai, Takehito Kozuka, Hideo Kitamura, Hideo Hashizume, Chiharu Kanegane, Koji Masuda, Kumiya Sugiyama, Reiko Tokuda, Junichi Furuta, Ikkou Higashimoto, Atsuko Kato, Mariko Seishima, Akihiko Tajiri, Atsuko Tomura, Hiroko Taniguchi, Hiroto Kojima, Hidenori Tanaka, Aiko Sakai, Wataru Morii, Masashi Nakamura, Yoichiro Kamatani, Atsushi Takahashi, Michiaki Kubo, Mayumi Tamari, Hirohisa Saito, Kayoko Matsunaga

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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 × 10−24 for rs9271588 and P = 2.96 × 10−24 for HLA-DQα1 amino acid position 34) and with the RBFOX1 locus at 16p13 (rs74575857, P = 8.4 × 10−9). 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 × 10−8). 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.

Original languageEnglish
Pages (from-to)1354-1363
Number of pages10
JournalJournal of Allergy and Clinical Immunology
Volume144
Issue number5
DOIs
Publication statusPublished - 11-2019

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Noguchi, E., Akiyama, M., Yagami, A., Hirota, T., Okada, Y., Kato, Z., Kishikawa, R., Fukutomi, Y., Hide, M., Morita, E., Aihara, M., Hiragun, M., Chinuki, Y., Okabe, T., Ito, A., Adachi, A., Fukunaga, A., Kubota, Y., Aoki, T., ... Matsunaga, K. (2019). HLA-DQ and RBFOX1 as susceptibility genes for an outbreak of hydrolyzed wheat allergy. Journal of Allergy and Clinical Immunology, 144(5), 1354-1363. https://doi.org/10.1016/j.jaci.2019.06.034