title: A possible association of EMID2 polymorphisms with aspirin hypersensitivity in asthma.
abstract: 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 (FEV(1)) 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 FEV(1) 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.
authors.affiliation: Department of Life Science, Sogang University, 1 Shinsu-dong, Mapo-gu, Seoul, 121-742, Republic of Korea.
authors.forename: Charisse Flerida A
authors.initials: CF
authors.lastname: Pasaje
authors.forename: Jeong-Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Byung-Lae
authors.initials: BL
authors.lastname: Park
authors.forename: Hyun Sub
authors.initials: HS
authors.lastname: Cheong
authors.forename: Mi-Kyeong
authors.initials: MK
authors.lastname: Kim
authors.forename: Inseon S
authors.initials: IS
authors.lastname: Choi
authors.forename: Sang Heon
authors.initials: SH
authors.lastname: Cho
authors.forename: Chein-Soo
authors.initials: CS
authors.lastname: Hong
authors.forename: Yong Won
authors.initials: YW
authors.lastname: Lee
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Lee
authors.forename: In Song
authors.initials: IS
authors.lastname: Koh
authors.forename: Tae-Joon
authors.initials: TJ
authors.lastname: Park
authors.forename: Jin-Sol
authors.initials: JS
authors.lastname: Lee
authors.forename: Yongha
authors.initials: Y
authors.lastname: Kim
authors.forename: Joon Seol
authors.initials: JS
authors.lastname: Bae
authors.forename: Choon-Sik
authors.initials: CS
authors.lastname: Park
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000150:complications* / Q000235:genetics*; D016022:Case-Control Studies; D002874:Chromosome Mapping; D003094:Collagen / Q000235:genetics*; D004342:Drug Hypersensitivity / Q000150:complications* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea; D055815:Young Adult
chemical_list: D003094:Collagen; D001241:Aspirin