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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:144

Article

Noguchi, Emiko¹  Akiyama, Masato^2,3  Yagami, Akiko⁴  Hirota, Tomomitsu^5,6  Okada, Yukinori^7,8  Kato, Zenichiro^9,10  Kishikawa, Reiko¹¹  Fukutomi, Yuma¹²  Hide, Michihiro¹³  Morita, Eishin¹⁴  Aihara, Michiko¹⁵  Hiragun, Makiko¹³  Chinuki, Yuko¹⁴  Okabe, Takahiro¹⁶  Ito, Akiko¹⁷  Adachi, Atsuko¹⁸  Fukunaga, Atsushi¹⁹  Kubota, Yumiko²⁰  Aoki, Toshiyuki²¹  Aoki, Youko²²  Nishioka, Kazue²³  Adachi, Tetsuya²⁴  Kanazawa, Nobuo²⁵  Miyazawa, Hitoshi²⁶  Sakai, Hiroyuki²⁷  Kozuka, Takehito²⁸  Kitamura, Hideo²⁹  Hashizume, Hideo³⁰  Kanegane, Chiharu³¹  Masuda, Koji³²  Sugiyama, Kumiya³³  Tokuda, Reiko³⁴  Furuta, Junichi³⁵  Higashimoto, Ikkou³⁶  Kato, Atsuko³⁷  Seishima, Mariko³⁸  Tajiri, Akihiko³⁹  Tomura, Atsuko⁴⁰  Taniguchi, Hiroko⁴¹  Kojima, Hiroto⁴²  Tanaka, Hidenori⁴²  Sakai, Aiko⁴³  Morii, Wataru¹  Nakamura, Masashi⁴⁴  Kamatani, Yoichiro^2,45  Takahashi, Atsushi^2,46  Kubo, Michiaki⁴⁷  Tamari, Mayumi^5,6  Saito, Hirohisa⁴⁸  Matsunaga, Kayoko⁴⁴ 

[1] Univ Tsukuba, Fac Med, Dept Med Genet, 1-1-1 Tennoudai, Tsukuba, Ibaraki 3058575, Japan

[2] RIKEN Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan

[3] Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Fukuoka, Fukuoka, Japan

[4] Fujita Hlth Univ, Sch Med, Dept Allergol, Nagoya, Aichi, Japan

[5] RIKEN Ctr Integrat Med Sci, Lab Resp & Allerg Dis, Yokohama, Kanagawa, Japan

[6] Jikei Univ, Sch Med, Res Ctr Med Sci, Core Res Facil Basic Sci Mol Genet, Tokyo, Japan

[7] Osaka Univ, Grad Sch Med, Dept Stat Genet, Osaka, Japan

[8] Osaka Univ, Immunol Frontier Res Ctr WPI IFReC, Lab Stat Immunol, Osaka, Japan

[9] Gifu Univ, United Grad Sch Drug Discovery & Med Informat Sci, Struct Med, Gifu, Japan

[10] Gifu Univ, Grad Sch Med, Dept Pediat, Gifu, Japan

[11] Natl Hosp Org Fukuoka Natl Hosp, Dept Allergol, Fukuoka, Fukuoka, Japan

[12] Natl Hosp Org Sagamihara Hosp, Clin Res Ctr Allergy & Rheumatol, Sagamihara, Kanagawa, Japan

[13] Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Dept Dermatol, Hiroshima, Japan

[14] Shimane Univ, Fac Med, Dept Dermatol, Izumo, Shimane, Japan

[15] Yokohama City Univ, Sch Med, Dept Dermatol, Yokohama, Kanagawa, Japan

[16] Okabe Allergy Clin, Fukuoka, Fukuoka, Japan

[17] Niigata Univ, Med & Dent Hosp, Dept Dermatol, Niigata, Japan

[18] Hyogo Prefectural Kakogawa Hosp, Dept Dermatol, Kakogawa, Hyogo, Japan

[19] Kobe Univ, Grad Sch Med, Dept Internal Related, Div Dermatol, Kobe, Hyogo, Japan

[20] Fukuoka Sanno Hosp, Dept Dermatol, Fukuoka, Fukuoka, Japan

[21] Aoki Skin & Allergy Clin Itchy Skin Dis, Osaka, Japan

[22] Aoki Dermatol, Miyazaki, Japan

[23] Joy Dermatol Clin, Sanyo Onoda, Japan

[24] Musashino Allergy Clin, Tokyo, Japan

[25] Wakayama Med Univ, Dept Dermatol, Wakayama, Japan

[26] Nishi Sapporo Skin & Allergy Clin, Sapporo, Hokkaido, Japan

[27] Asahikawa City Hosp, Dept Dermatol, Asahikawa, Hokkaido, Japan

[28] Hino Clin, Dermatol Sect, Sakai, Osaka, Japan

[29] Aomori Prefectural Cent Hosp, Dept Dermatol, Aomori, Japan

[30] Shimada Municipal Hosp, Dept Dermatol, Shimada, Japan

[31] Natl Hosp Org Toyama Hosp, Dept Allergy, Toyama, Japan

[32] Kyoto Prefectural Univ Med, Dept Dermatol, Kyoto, Japan

[33] Dokkyo Med Univ, Saitama Med Ctr, Dept Resp Med & Clin Immunol, Koshigaya, Japan

[34] Natl Mie Hosp, Tsu, Mie, Japan

[35] Univ Tsukuba, Fac Med, Dept Dermatol, Tsukuba, Ibaraki, Japan

[36] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Pulm Med, Kagoshima, Japan

[37] Osaka Kaisei Hosp, Dept Dermatol, Osaka, Japan

[38] Gifu Univ, Grad Sch Med, Dept Dermatol, Gifu, Japan

[39] Tajiri Dermatol Clin, Miyazaki, Japan

[40] Tomura Clin Dermatol, Akita, Japan

[41] Kudanzaka Hosp, Dept Dermatol, Tokyo, Japan

[42] HLA Fdn Lab, Kyoto, Japan

[43] Univ Tsukuba, Fac Med, Dept Child Hlth, Tsukuba, Ibaraki, Japan

[44] Fujita Hlth Univ, Sch Med, Dept Integrat Med Sci Allerg Dis, Nagoya, Aichi, Japan

[45] Kyoto Univ, Grad Sch Med, Kyoto McGill Int Collaborat Sch Genom Med, Kyoto, Japan

[46] Natl Cerebral & Cardiovas Ctr, Dept Genom Med, Res Inst, Osaka, Japan

[47] RIKEN Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan

[48] Natl Res Inst Child Hlth & Dev, Dept Allergy & Clin Immunol, Tokyo, Japan

关键词: Hydrolyzed wheat protein;    allergy;    percutaneous;    genome-wide association study;    HLA;    RBFOX1;   

DOI  :  10.1016/j.jaci.2019.06.034

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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