Friday, 16 October 2015
Hall D1 Foyer (Floor 3) (Coex Convention Center)
Background: Common clinical syndromes of aspirin hypersensitivity, aspirin-exacerbated respiratory disease (AERD) and aspirin-exacerbated cutaneous disease (AECD), was subjected to a genome-wide association study to identify differential genetic biomarkers 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, 211 AECD patients and 1989 healthy normal control subjects (NC) revealed SNPs on chromosome 2 and 6 that were associated with AERD, not AECD. To validate the association, we enrolled a second cohort comprising AERD, normal healthy control and disease-control (aspirin tolerant asthma; ATA) groups. A diagnostic value was evaluated by the area under the curve (AUC) value of receiver operating characteristic (ROC) curves for each combination. Results: Three SNPs of DPP10 gene on chromosome 2 and two SNPs of HLA-DPB1 gene on chromosome 6 showed a significant association with the AERD phenotype. 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 the patients harboring the A allele of a particular SNP, rs3128965, in the HLA-DPB1 region showed increased bronchial hyperresponsiveness to inhaled aspirin, methacholine, and higher 15-HETE levels, than those without the A allele. Three intronic SNPs of DPP10 gene are significantly associated with the AERD phenotype. Serum DPP10 level was significantly higher in AERD compared to control groups, ATA and NC. A combination of SNP of DPP10 gene and serum DPP10 level showed a good diagnostic value in a close correlation with c-Kit and YKL. Conclusions: This implies the potential of two SNPs, rs3128965 of HLA-DPB1, rs17048175 of DPP10, as genetic biomarkers for the AERD phenotype.