title: The SNP rs3128965 of HLA-DPB1 as a genetic marker of the AERD phenotype.
abstract: BACKGROUND
  Two common clinical syndromes of acetylsalicylic acid (aspirin) hypersensitivity, aspirin-exacerbated respiratory disease (AERD) and aspirin-exacerbated cutaneous disease (AECD), were subjected to a genome-wide association study to identify strong genetic markers for aspirin hypersensitivity in a Korean population.
  
  
  METHODS
  A comparison of SNP genotype frequencies on an Affymetrix Genome-Wide Human SNP array of 179 AERD patients and 1989 healthy normal control subjects (NC) revealed SNPs on chromosome 6 that were associated with AERD, but not AECD. To validate the association, we enrolled a second cohort comprising AERD (n = 264), NC (n = 238) and disease-control (aspirin tolerant asthma; ATA, n = 387) groups.
  
  
  RESULTS
  The minor genotype frequency (AG or AA) of a particular SNP, rs3128965, in the HLA-DPB1 region was higher in the AERD group compared to the ATA or NC group (P = 0.001, P = 0.002, in a co-dominant analysis model, respectively). Comparison of rs3128965 alleles with the clinical features of asthmatics revealed that patients harboring the A allele had increased bronchial hyperresponsiveness to inhaled aspirin and methacholine, and higher 15-HETE levels, than those without the A allele (P = 0.039, 0.037, and 0.004, respectively).
  
  
  CONCLUSIONS
  This implies the potential of rs3128965 as a genetic marker for diagnosis and prediction of the AERD phenotype.
authors.affiliation: Department of Allergy & Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Allergy & Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Bo-Young
authors.initials: BY
authors.lastname: Cho
authors.affiliation: Department of Allergy & Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Hyunna
authors.initials: H
authors.lastname: Choi
authors.affiliation: DNA link, Inc., Seoul, Korea.
authors.forename: Eun-Soon
authors.initials: ES
authors.lastname: Shin
authors.affiliation: Department of Allergy & Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Young-Min
authors.initials: YM
authors.lastname: Ye
authors.affiliation: DNA link, Inc., Seoul, Korea.
authors.forename: Jong-Eun
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Department of Allergy & Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Hae-Sim
authors.initials: HS
authors.lastname: Park
mesh_terms: D000328:Adult; D055963:Asthma, Aspirin-Induced / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study; D059868:HLA-DP beta-Chains / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen