1. HLA-DQ and RBFOX1 as susceptibility genes for an outbreak of hydrolyzed wheat allergy
- Author
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Zenichiro Kato, Takehito Kozuka, Tetsuya Adachi, Reiko Tokuda, Mariko Seishima, Junichi Furuta, Emiko Noguchi, Michihiro Hide, Koji Masuda, Masashi Nakamura, Hirohisa Saito, Yukinori Okada, Tomomitsu Hirota, Ikkou Higashimoto, Hidenori Tanaka, Yoichiro Kamatani, Takahiro Okabe, Masato Akiyama, Yuma Fukutomi, Hitoshi Miyazawa, Eishin Morita, Akiko Ito, Toshiyuki Aoki, Aiko Sakai, Yumiko Kubota, Michiaki Kubo, Akihiko Tajiri, Atsushi Takahashi, Kayoko Matsunaga, Makiko Hiragun, Mayumi Tamari, Atsuko Kato, Kazue Nishioka, Kumiya Sugiyama, Yuko Chinuki, Youko Aoki, Atsuko Tomura, Atsushi Fukunaga, Hideo Kitamura, Reiko Kishikawa, Hideo Hashizume, Hiroko Taniguchi, Hiroto Kojima, Hiroyuki Sakai, Chiharu Kanegane, Atsuko Adachi, Akiko Yagami, Wataru Morii, Nobuo Kanazawa, and Michiko Aihara
- Subjects
0301 basic medicine ,Male ,Allergy ,Genotype ,Immunology ,Single-nucleotide polymorphism ,Human leukocyte antigen ,Wheat Hypersensitivity ,Biology ,Polymorphism, Single Nucleotide ,Disease Outbreaks ,03 medical and health sciences ,0302 clinical medicine ,Gene Frequency ,Japan ,Food allergy ,HLA-DQ Antigens ,Genetic variation ,HLA-DQ ,medicine ,Immunology and Allergy ,Humans ,Genetic Predisposition to Disease ,Genotyping ,Triticum ,Genetics ,Hydrolysis ,Allergens ,Antigens, Plant ,Middle Aged ,medicine.disease ,030104 developmental biology ,030228 respiratory system ,Female ,RNA Splicing Factors ,Wheat allergy ,Genome-Wide Association Study - 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 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.
- Published
- 2018