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A possible association of EMID2 polymorphisms with aspirin hypersensitivity in asthma

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Aspirin-intolerant asthma (AIA) is an asthma phenotype characterized by the development of bronchoconstriction following ingestion of aspirin. Despite the well-defined pathological trigger, the underlying mechanisms of AIA are still unclear. With the biophysical characteristics of the human EMI domain-containing protein 2 (EMID2) gene in relation to the extracellular matrix deposition and epithelial-mesenchymal transition as pivotal characteristics of airway remodeling in asthma, we hypothesized that genetic polymorphisms of EMID2 might affect the development of AIA. In this study, the allelic associations of 49 single-nucleotide polymorphisms (SNPs) of the human EMID2 gene were evaluated from 163 AIA patients and 429 aspirin-tolerant asthma (ATA) subjects as controls in a Korean population. Logistic analysis showed that five SNPs (P = 0.01–0.04, but P corr > 0.05) and EMID2_BL2_ht2 haplotype (unique to the minor alleles of rs4727494 and rs13233066; P = 0.02; P corr = 0.02) were significantly associated with AIA. More interestingly, regression analysis of the decline of forced expiratory volume in one second (FEV1) by aspirin provocation revealed that 10 SNPs (P = 0.003–0.04) and four relevant haplotypes (P = 0.002–0.02) were significantly associated with the fall rate of FEV1 by aspirin provocation, indicating that genetic polymorphisms of EMID2 could cause meaningful deficits in the upper and lower airways among AIA patients. These findings provide evidence that EMID2 may be a susceptible genetic factor for aspirin hypersensitivity among asthmatics in Korean population.

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Aspirin-intolerant asthma


EMI domain-containing protein 2


Non-steroidal inflammatory drugs


Extracellular matrix


Global Initiative for Asthma


Angiotensin converting enzyme


Sequence detection system


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This work was supported by a grant from the Korea Health 21 R&D Project (A010249); a grant number M1-0302-00-0073 from Korea Science and Engineering Foundation (KOSEF) funded by the Korea government (MEST) (No. 2009-0080157); an Intramural Research Grant of the Korea National Institute of Health (grant number 4800-4845-300-260-00); an Intramural Research Grant from Sogang University (grant number 200810021.01); and a Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009-0093822). The DNA samples were generously provided by Soonchunhyang University, Bucheon Hospital Biobank, a member of the National Biobank of Korea, supported by the Ministry of Health, Welfare and Family Affairs, Republic of Korea.

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The authors declare no conflict of interests.

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Correspondence to Choon-Sik Park or Hyoung Doo Shin.

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Supplementary Table 1

Variants of EMID2 included in this study (DOC 67 kb)

Supplementary Table 2

Logistic analysis of the SNPs in EMID2 between AIA and ATA patients (DOC 122 kb)

Supplementary Table 3

Logistic analysis of the haplotypes in EMID2 between AIA and ATA patients (DOC 50 kb)

Supplementary Table 4

Association analysis between SNPs of EMID2 gene and the fall of FEV1 by aspirin provocation (DOC 79 kb)

Supplementary Table 5

Association analysis between haplotypes of EMID2 gene and the fall of FEV1 by aspirin provocation (DOC 47 kb)

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Pasaje, C.F.A., Kim, JH., Park, BL. et al. A possible association of EMID2 polymorphisms with aspirin hypersensitivity in asthma. Immunogenetics 63, 13–21 (2011).

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