title: Potential association of DDR1 genetic variant with FEV1 decline by aspirin provocation in asthmatics.
abstract: BACKGROUND
  The discoidin domain receptor tyrosine kinase 1 (DDR1) is positioned within the major histocompatibility complex (MHC) region which plays an important role in the immune system. In addition, DDR1 has been elucidated to be downregulated during the epithelial-mesenchymal transition of bronchial epithelium.
  
  
  OBJECTIVE
  To investigate the potential genetic associations between DDR1 and aspirin-exacerbated respiratory disease (AERD), this study conducted association studies of DDR1 single nucleotide polymorphisms (SNPs) with AERD and the obstructive symptom of forced expiratory volume in 1 s (FEV(1)) decline after aspirin provocation.
  
  
  METHODS
  Nine common SNPs were genotyped in 93 AERD patients and 96 aspirin-tolerant asthma (ATA) controls. The genotype distributions of all loci were in Hardy-Weinberg equilibrium (HWE; p > .05). Results. In the results of logistic analyses using age, sex, smoking status, and atopy as covariates, DDR1 rs1264320 in the intronic region showed a potent association signal with FEV(1) decline by aspirin provocation in asthmatics of this study even after corrections for multiple testing (p = .003 and corrected p = .01). However, the variants of DDR1 were not significantly associated with the AERD development (corrected p > .05). On further comparison of FEV(1) decline by aspirin provocation between AERD and ATA, the variant rs1264320 was found to be associated with the FEV(1) decline of ATA rather than AERD.
  
  
  CONCLUSIONS
  Despite the need for further functional evaluations and replications, we conclude that DDR1 polymorphisms are not likely to contribute to predispositions of AERD, but may be potentially associated with FEV(1) decline by aspirin provocation in asthmatics.
authors.affiliation: Department of Life Science, Sogang University, Seoul, Republic of Korea.
authors.forename: Jason Yongha
authors.initials: JY
authors.lastname: Kim
authors.forename: Jeong-Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Byung-Lae
authors.initials: BL
authors.lastname: Park
authors.forename: Charisse Flerida A
authors.initials: CF
authors.lastname: Pasaje
authors.forename: Joon Seol
authors.initials: JS
authors.lastname: Bae
authors.forename: Soo-Taek
authors.initials: ST
authors.lastname: Uh
authors.forename: Yong-Hoon
authors.initials: YH
authors.lastname: Kim
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: Byoung Whui
authors.initials: BW
authors.lastname: Choi
authors.forename: Jong Sook
authors.initials: JS
authors.lastname: Park
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; D001241:Aspirin / Q000008:administration & dosage; D001249:Asthma / Q000235:genetics / Q000503:physiopathology; D055963:Asthma, Aspirin-Induced / Q000235:genetics* / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D000070819:Discoidin Domain Receptor 1; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology*; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007438:Introns / Q000235:genetics; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016366:Open Reading Frames / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D055815:Young Adult
chemical_list: C092030:DDR1 protein, human; D000070819:Discoidin Domain Receptor 1; D020794:Receptor Protein-Tyrosine Kinases; D001241:Aspirin