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

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

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Wheat Hypersensitivity
HLA-DQ Antigens
Disease Outbreaks
Genes
Genome-Wide Association Study
Proteins
Amino Acids
Triticum
Single Nucleotide Polymorphism
Soaps
Food Hypersensitivity
Japan
Hypersensitivity
Genome

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Noguchi, Emiko ; Akiyama, Masato ; Yagami, Akiko ; Hirota, Tomomitsu ; Okada, Yukinori ; Kato, Zenichiro ; Kishikawa, Reiko ; Fukutomi, Yuma ; Hide, Michihiro ; Morita, Eishin ; Aihara, Michiko ; Hiragun, Makiko ; Chinuki, Yuko ; Okabe, Takahiro ; Ito, Akiko ; Adachi, Atsuko ; Fukunaga, Atsushi ; Kubota, Yumiko ; Aoki, Toshiyuki ; Aoki, Youko ; Nishioka, Kazue ; Adachi, Tetsuya ; Kanazawa, Nobuo ; Miyazawa, Hitoshi ; Sakai, Hiroyuki ; Kozuka, Takehito ; Kitamura, Hideo ; Hashizume, Hideo ; Kanegane, Chiharu ; Masuda, Koji ; Sugiyama, Kumiya ; Tokuda, Reiko ; Furuta, Junichi ; Higashimoto, Ikkou ; Kato, Atsuko ; Seishima, Mariko ; Tajiri, Akihiko ; Tomura, Atsuko ; Taniguchi, Hiroko ; Kojima, Hiroto ; Tanaka, Hidenori ; Sakai, Aiko ; Morii, Wataru ; Nakamura, Masashi ; Kamatani, Yoichiro ; Takahashi, Atsushi ; Kubo, Michiaki ; Tamari, Mayumi ; Saito, Hirohisa ; Matsunaga, Kayoko. / HLA-DQ and RBFOX1 as susceptibility genes for an outbreak of hydrolyzed wheat allergy. In: Journal of Allergy and Clinical Immunology. 2019 ; Vol. 144, No. 5. pp. 1354-1363.
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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.",
author = "Emiko Noguchi and Masato Akiyama and Akiko Yagami and Tomomitsu Hirota and Yukinori Okada and Zenichiro Kato and Reiko Kishikawa and Yuma Fukutomi and Michihiro Hide and Eishin Morita and Michiko Aihara and Makiko Hiragun and Yuko Chinuki and Takahiro Okabe and Akiko Ito and Atsuko Adachi and Atsushi Fukunaga and Yumiko Kubota and Toshiyuki Aoki and Youko Aoki and Kazue Nishioka and Tetsuya Adachi and Nobuo Kanazawa and Hitoshi Miyazawa and Hiroyuki Sakai and Takehito Kozuka and Hideo Kitamura and Hideo Hashizume and Chiharu Kanegane and Koji Masuda and Kumiya Sugiyama and Reiko Tokuda and Junichi Furuta and Ikkou Higashimoto and Atsuko Kato and Mariko Seishima and Akihiko Tajiri and Atsuko Tomura and Hiroko Taniguchi and Hiroto Kojima and Hidenori Tanaka and Aiko Sakai and Wataru Morii and Masashi Nakamura and Yoichiro Kamatani and Atsushi Takahashi and Michiaki Kubo and Mayumi Tamari and Hirohisa Saito and Kayoko Matsunaga",
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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, Aoki, Y, Nishioka, K, Adachi, T, Kanazawa, N, Miyazawa, H, Sakai, H, Kozuka, T, Kitamura, H, Hashizume, H, Kanegane, C, Masuda, K, Sugiyama, K, Tokuda, R, Furuta, J, Higashimoto, I, Kato, A, Seishima, M, Tajiri, A, Tomura, A, Taniguchi, H, Kojima, H, Tanaka, H, Sakai, A, Morii, W, Nakamura, M, Kamatani, Y, Takahashi, A, Kubo, M, Tamari, M, Saito, H & Matsunaga, K 2019, 'HLA-DQ and RBFOX1 as susceptibility genes for an outbreak of hydrolyzed wheat allergy', Journal of Allergy and Clinical Immunology, vol. 144, no. 5, pp. 1354-1363. https://doi.org/10.1016/j.jaci.2019.06.034

HLA-DQ and RBFOX1 as susceptibility genes for an outbreak of hydrolyzed wheat allergy. / Noguchi, Emiko; Akiyama, Masato; Yagami, Akiko; Hirota, Tomomitsu; Okada, Yukinori; Kato, Zenichiro; Kishikawa, Reiko; Fukutomi, Yuma; Hide, Michihiro; Morita, Eishin; Aihara, Michiko; Hiragun, Makiko; Chinuki, Yuko; Okabe, Takahiro; Ito, Akiko; Adachi, Atsuko; Fukunaga, Atsushi; Kubota, Yumiko; Aoki, Toshiyuki; Aoki, Youko; Nishioka, Kazue; Adachi, Tetsuya; Kanazawa, Nobuo; Miyazawa, Hitoshi; Sakai, Hiroyuki; Kozuka, Takehito; Kitamura, Hideo; Hashizume, Hideo; Kanegane, Chiharu; Masuda, Koji; Sugiyama, Kumiya; Tokuda, Reiko; Furuta, Junichi; Higashimoto, Ikkou; Kato, Atsuko; Seishima, Mariko; Tajiri, Akihiko; Tomura, Atsuko; Taniguchi, Hiroko; Kojima, Hiroto; Tanaka, Hidenori; Sakai, Aiko; Morii, Wataru; Nakamura, Masashi; Kamatani, Yoichiro; Takahashi, Atsushi; Kubo, Michiaki; Tamari, Mayumi; Saito, Hirohisa; Matsunaga, Kayoko.

In: Journal of Allergy and Clinical Immunology, Vol. 144, No. 5, 11.2019, p. 1354-1363.

Research output: Contribution to journalArticle

TY - JOUR

T1 - HLA-DQ and RBFOX1 as susceptibility genes for an outbreak of hydrolyzed wheat allergy

AU - Noguchi, Emiko

AU - Akiyama, Masato

AU - Yagami, Akiko

AU - Hirota, Tomomitsu

AU - Okada, Yukinori

AU - Kato, Zenichiro

AU - Kishikawa, Reiko

AU - Fukutomi, Yuma

AU - Hide, Michihiro

AU - Morita, Eishin

AU - Aihara, Michiko

AU - Hiragun, Makiko

AU - Chinuki, Yuko

AU - Okabe, Takahiro

AU - Ito, Akiko

AU - Adachi, Atsuko

AU - Fukunaga, Atsushi

AU - Kubota, Yumiko

AU - Aoki, Toshiyuki

AU - Aoki, Youko

AU - Nishioka, Kazue

AU - Adachi, Tetsuya

AU - Kanazawa, Nobuo

AU - Miyazawa, Hitoshi

AU - Sakai, Hiroyuki

AU - Kozuka, Takehito

AU - Kitamura, Hideo

AU - Hashizume, Hideo

AU - Kanegane, Chiharu

AU - Masuda, Koji

AU - Sugiyama, Kumiya

AU - Tokuda, Reiko

AU - Furuta, Junichi

AU - Higashimoto, Ikkou

AU - Kato, Atsuko

AU - Seishima, Mariko

AU - Tajiri, Akihiko

AU - Tomura, Atsuko

AU - Taniguchi, Hiroko

AU - Kojima, Hiroto

AU - Tanaka, Hidenori

AU - Sakai, Aiko

AU - Morii, Wataru

AU - Nakamura, Masashi

AU - Kamatani, Yoichiro

AU - Takahashi, Atsushi

AU - Kubo, Michiaki

AU - Tamari, Mayumi

AU - Saito, Hirohisa

AU - Matsunaga, Kayoko

PY - 2019/11

Y1 - 2019/11

N2 - 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.

AB - 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.

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