4.7 Article

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

Journal

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 144, Issue 5, Pages 1354-1363

Publisher

MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2019.06.034

Keywords

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

Funding

  1. AMED [15ek0410010h0002]
  2. JSPS KAKENHI of the Japan Society for the Promotion of Science [17H05786]
  3. BioBank Japan project by the Ministry of Education, Culture, Sports, Sciences and Technology of the Japanese government
  4. BioBank Japan project by the Ministry of Education, Culture, Sports, Sciences and Technology of the Japan Agency for Medical Research and Development
  5. Grants-in-Aid for Scientific Research [17H05786] Funding Source: KAKEN

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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.

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